Notes
J . Org. Chem., Vol. 65, No. 16, 2000 5041
MHz, DMSO-d6) δ 155.4, 77.6, 57.0, 31.8, 28.2, 19.2, 17.8, 11.8;
IR (KBr) 3330, 2962, 1670, and 1520 cm-1; [R]25D -4.00 (c 9.997,
di-tert-butyl dicarbonate (16.37 g, 75.0 mmol) in chloroform (35
mL). After 16 h the reaction mixture was extracted with 15%
(v/v) aqueous phosphoric acid (2×), brine (1×), dilute aqueous
sodium bicarbonate (1×), and water (1×). The organic phase was
dried (Na2SO4), filtered through a 1 in. pad of silica gel, and
evaporated to give 17.24 g of a white solid (86%): 1H NMR (300
MHz, DMSO-d6) δ 9.09 (s,1H), 6.95 (d, J ) 8.5 Hz, 2H), 6.63 (d,
J ) 8.5 Hz, 2H), 6.48 (d, J ) 8.3 Hz, 1H), 4.61 (t, J ) 5.6 Hz,
1H), 3.47 (m, 1H), 3.28 (m, 2H), 2.65 (ABX m, 1H), 2.47 (ABX
MeOH); MS, (+)ESI, m/z 314, [M + H]+. Anal. Calcd for C10H20
-
INO2: C, 38.35; H, 6.44; N, 4.47. Found: C, 38.52; H, 6.52; N,
4.42.
ter t-Bu tyl (1R)-1,2-Dim eth ylp r op yl Ca r ba m a te (11d ).
The procedure used here was identical to that for 11a . The
starting material 10d (2.39 g, 7.63 mmol) yielded 1.32 g (92%)
of the title compound as a clear crystalline solid: mp 35-36 °C;
1H NMR (300 MHz, DMSO-d6) δ 6.57 (d, J ) 8.5, 1H), 3.23-
3.28 (m, 1H), 1.52-1.60 (m, 1H), 1.36 (s, 9H), 0.93 (d, J ) 6.6,
3H), 0.79 (dd, J ) 3.4, 6.8; 6H); 13C NMR (100 MHz, DMSO-d6)
m, 1H), and 1.32 (s, 9H); MS(ESI(-)), [M - H]- at m/z 266; [R]25
D
-25.00 (c 10.0, MeOH).
Met h yl 2-[(4-{(2S)-2-[(ter t-Bu t oxyca r b on yl)a m in o]-3-
h yd r oxyp r op yl}p h en oxy)m eth yl]ben zoa te (14f). A mixture
of N-t-Boc-L-tyrosinol (9f) (15.50 g, 58.0 mmol), bromomethyl
2-methylbenzoate (13.30 g, 58.0 mmol), potassium carbonate
(8.02 g, 58.0 mmol), and potassium iodide (250 mg) in acetoni-
trile/acetone (75 mL/25 mL) was heated to reflux for 14 h. The
cooled reaction mixture was cooled and filtered. The organic
phase was washed with aqueous sodium thiosulfate, H2O, and
brine (1× each), dried (Na2SO4), filtered, and evaporated to leave
a yellow solid. The product was purified by crystallization from
hexane/ethyl acetate to afford 20.00 g (83%) as a white solid with
mp 102-4 °C: 1H NMR (400 MHz, CDCl3) δ 8.02 (dd, J ) 7.9
and 1.5 Hz, 1H), 7.74 (dd, J ) 7.9 and 0.6 Hz, 1H), 7.55 (dt, J )
7.5 and 1.5 Hz), 7.37 (dt, J ) 8.6 and 0.6 Hz), 7.12 (d, J ) 8.6
Hz, 2H), 6.92 (d, J ) 8.6 Hz, 2H), 5.48 (s, 2H), 4.70 (br, 1H),
3.90 (s, 3H), 3.82 (br, 1H), 3.66 (ABX m, 1H), 3.56 (ABX m, 1H),
2.77 (d, J ) 7.0 Hz, 2H), and 1.42 (s, 9H); 13C NMR (100 MHz,
DMSO-d6) δ 166.9, 156.5, 155.1, 138.4, 132.3, 131.6, 130.10,
130.07, 128.5, 128.0, 127.7, 114.3, 77.3, 67.5, 62.8, 54.0, 52.1,
35.9, 28.2; IR (KBr) 1723, 1684, and 1529 cm-1; MS(EI), [M+]
δ 155.1, 77.1, 50.9, 32.7,28.3, 18.8, 18.5, 17.3; [R]25 -8.00; IR
D
(KBr) 3300, 2970, 1669, and 1532 cm-1; MS, (+)APCI, [M + H]+
m/z 188. Anal. Calcd for C10H21NO2: C, 64.13; H, 11.30; N, 7.48.
Found: C, 64.14; H, 11.50; N, 7.45.
(1R)-1,2-Dim eth ylp r op yla m in e (12d ). The procedure used
for 12a (above) was carried out using 0.46 g (2.46 mmol) of 11d
to yield 0.27 g (89%) of the title compound as white needle-
shaped crystals: mp 218 °C; 1H NMR (300 MHz, DMSO-d6) δ
8.07 (s broad, 3H), 2.93-2.99 (m, 1H), 1.79-1.87 (m, 1H), 2.21
(d, J ) 6.6, 3H), 0.88 (dd, J ) 6.8, 10.5; 6H); 13C NMR (100 MHz,
DMSO-d6) δ 51.6, 30.7, 18.8, 16.9, 14.5; IR (KBr) 2885, 1604,
1515 cm-1; [R]25 +2.00 (c 10.004, MeOH); MS, (+)APCI, m/z
D
88, [M + H]+. Anal. Calcd for C5H14ClN: C, 48.58; H, 11.41; N,
11.33. Found: C, 48.70; H, 11.57; N, 11.32.
D-Va lin ol (8c). The representative procedure found for 8a
(above) was followed using L-valine (5.0 g, 42.7 mmol) to yield
4.04 g of a colorless oil (92%). The NMR, IR, and MS data are
identical to those shown for 8d (above). [R]25 -14.03 (c 9.980,
D
MeOH). Anal. Calcd for C5H13NO: C, 58.21; H, 12.70; N, 13.58.
Found: C,58.11; H,12.55; N,13.49.
at m/z 415; [R]25D -15.52 (c 6.70, MeOH). Anal. Calcd for C23H29
-
N-t-Boc-D-va lin ol (9c). The representative procedure found
for 9a (above) was followed using d-valinol (5.0 g; 48.5 mmol).
The procedure yielded 9.84 g (99%) of the title compound as a
clear, colorless oil. The NMR, IR, and MS data are identical to
NO6: C, 66.49; H, 7.04; N, 3.37. Found: C, 66.18; H, 7.18; N,
3.42.
Met h yl 2-[(4-{(2S)-2-[(ter t-Bu t oxyca r b on yl)a m in o]-3-
iod op r op yl}p h en oxy)m eth yl]ben zoa te (15f). The represen-
tative procedure for 10a (above) was employed with 14f (1.16 g,
2.79 mmol) of the alcohol yielded 1.00 g (68%) of the title
compound as white crystals: mp 63-71 °C; 1H NMR (300 MHz,
DMSO-d6) δ 7.88-7.90 (m, 1H), 7.58-7.65 (m, 2), 7.43-7.47 (m,
1H), 7.12 (d, 2H), 6.98 (d, 1H), 6.88 (d, 2H), 5.36 (s, 2H), 3.79 (s,
3H), 3.54 (m, 1H) 3.31-3.33 (m, 1H), 3.14-3.18 (m, 1H), 2.71-
2.76 (m, 1H), 2.61-2.63 (m, 1H), 1.24-1.47 (m, 9H); 13C NMR
(100 MHz, DMSO-d6) δ 166.9, 158.6, 157.0, 156.8, 154.9, 138.3,
138.2, 130.6, 130.5, 130.1, 130.0, 128.8, 128.6, 128.5, 128.1, 128.0,
127.8, 127.6, 114.6, 114.5, 110.8, 77.8, 68.0, 67.5, 53.2, 52.6, 52.1,
those shown for 9d (above). [R]25 +14.99 (c 10.004, MeOH).
D
Anal. Calcd for C10H21NO3: C, 59.09; H, 10.41; N, 6.89. Found:
C, 59.06; H, 10.39; N, 6.71.
ter t-Bu tyl (1R)-1-(Iod om eth yl)-2-m eth ylp r op yl Ca r ba m -
a te (10c). The representative procedure for 10a (above) was
employed with 9c (4.06 g, 20.0 mmol) and yielded 5.26 g (84%)
of the title compound as a light-yellow crystalline solid: mp 68-
70 °C. The NMR, IR, and MS data are identical to those shown
for 10d (above). [R]25 +5.00 (c 10.001, MeOH). Anal. Calcd for
D
C
10H20INO2: C, 38.35; H, 6.44; N, 4.47. Found: C, 38.58; H, 6.66;
N, 4.39.
ter t-Bu tyl (1S)-1,2-Dim eth ylp r op yl Ca r ba m a te (11c). The
28.2, 27.9, 27.8, 23.9, 12.8; IR (KBr) 1718, 1688, and 1512 cm-1
;
[R]25 +7.37 (c 6.38, MeOH); MS, ESI(+), m/z 543, [M + NH4]+.
D
representative procedure for 11a (above) was carried out on 10c
(3.78 g; 12.1 mmol) and yielded 2.07 g (91%) of the title
compound as clear, colorless crystals: mp 35-37 °C. The NMR,
IR, and MS data are identical to those shown for 11d (above).
Anal. Calcd for C23H28INO5: C, 52.58; H, 5.37; N, 2.67. Found:
C, 52.41; H, 5.36; N, 2.57.
Meth yl 2-[(4-{(2R)-2-[(ter t-Bu toxycar bon yl)am in o]pr opyl}-
p h en oxy)m eth yl]ben zoa te (16f). The representative proce-
dure for 11a (above) was employed with 15f (0.32 g, 0.61 mmol)
for the iodo compound to yield 0.185 g (76%) of the title
compound as white crystals: 1H NMR (300 MHz, DMSO-d6) δ
7.88-7.90 (m, 1H), 7.58-7.65 (m, 2H), 7.43-7.47 (m, 1H), 7.06-
7.09 (m, 2H), 6.85-6.88 (m, 2H), 6.71 (d, J ) 8.5 Hz, 1H), 5.36
(s, 2H), 3.79 (m, 1H), 3.79 (s, 3H), 3.56-3.60 (m, 1H), 2.61-
2.66 (m, 1H), 2.44-2.46 (m, 1H), 1.33-1.35 (m, 9H), and 0.96
(d, J ) 6.6 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 166.9,
156.4, 154.8, 138.4, 132.3, 131.6, 130.1, 128.5, 128.0 (2C), 127.7
(2C), 114.3, 77.2, 67.5, 52.1, 47.6, 41.2, 28.2, 27.6, and 20.2; IR
(KBr) 1722, 1683, and 1512 cm-1; [R]25D -4.00 (c 9.993, MeOH);
MS, (+)ESI, m/z 400, [M + H]+. Anal. Calcd for C23H29NO5: C,
69.15; H, 7.32; N, 3.51. Found: C, 68.88; H, 7.45; N, 3.46.
Met h yl 2-({4-[(2R)-2-Am in op r op yl]p h en oxy}m et h yl)-
ben zoa te Hyd r och lor id e (17f). The representative procedure
for 12a (above) was carried out on 16f (0.13 g, 0.69 mmol) and
yielded 0.083 g (92%) of the title compound as a white solid: 1H
NMR (400 MHz, DMSO-d6) δ 7.89 (dd, J ) 7.8 and 1.0 Hz, 1H),
7.63 (m, 2H), 7.43 (dt, J ) 7.3 and 1.5 Hz, 1H), 7.07 (d, J ) 8.5
Hz, 2H), 6.87 (d, J ) 8.5 Hz, 2H), 5.36 (s, 2H), 3.79 (s, 3H), 2.93
(m, 1H), 2.43 (d, J ) 6.6 Hz, 2H), and 0.92 (d, J ) 6.1 Hz, 3H);
13C NMR (100 MHz, DMSO-d6) δ 166.9, 156.5, 138.4, 132.3,
130.1, 128.4, 128.0 (2C), 127.7 (2C), 114.3, 67.5, 52.1, 48.3, 45.3,
[R]25 +6.61 (c 7.41, MeOH). Anal. Calcd for C10H21NO2: C,
D
64.13; H, 11.30; N, 7.48. Found: C, 64.21; H, 11.40; N, 7.49.
(1S)-1,2-Dim eth ylp r op yla m in e Hyd r och lor id e (12c). The
representative procedure for 12a (above) was carried out on 11c
(0.13 g; 0.69 mmol) and yielded 0.083 (92%) of the title compound
as clear, colorless crystals: mp 35-37 °C. The NMR, IR, and
MS data are identical to those shown for 12d (above): mp 217-
218 °C; [R]25 -2.01 (c 9.946, MeOH). Anal. Calcd for C5H14
-
D
NCl: C, 48.58; H, 11.41; N, 11.33. Found: C, 48.63; H, 11.76;
N, 11.28.
Br om om eth yl 2-Meth ylben zoa te. A solution of 9.4 g (62.9
mmol) of methyl 2-methylbenzoate, 11.2 g (62.9 mmol) of
N-bromosuccinimide, and AIBN (2-3 mg) in carbon tetrachloride
(90 mL) was heated at 90 °C for 18 h. The solution was cooled
to 0 °C, and the solid was filtered from the solution. The organic
solution was washed twice with dilute aqueous Na2S2O3. The
CCl4 was evaporated at reduced pressure. The residue was taken
up in diethyl ether, dried over Na2SO4, and filtered through a 5
cm pad of silica gel rinsed with additional ether. Evaporation
gave 11.96 g (83%) of a clear colorless oil: 1H NMR (300 MHz,
CDCl3) δ 7.97 (dd, J ) 7.6 and 1.16 Hz, 1H), 7.48 (m, 2H), 7.39
(m, 1H), 4.96 (s, 2H), and 3.95 (s, 3H).
N-t-Boc-L-tyr osin ol (9f). To a room temperature mixture of
L-tyrosinol hydrochloride (15.278 g, 75.0 mmol) and triethy-
lamine (10.45 mL, 75.0 mmol) in chloroform (100 mL) was added
and 23.2; [R]25 -17.00 (c 10.00, MeOH); MS, (+)ESI, m/z 300
D
[M + H]+.