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M. Sailer et al.
Paper
Synthesis
mL), aq 1 M HCl (2 × 50 mL), H2O (100 mL) and brine (50 mL), and
dried (Na2SO4). Removal of hexanes under vacuum furnished the
products 1–8 in yields ranging from 86 to 95% (Table 1).
1H NMR (300 MHz, CDCl3): δ = 0.87 (t, J = 6.7 Hz, 3 H), 1.27 (m, 15 H),
2.38 (dd, J = 9.0, 16.3 Hz, 1 H), 2.50 (dd, J = 3.5, 16.1 Hz, 1 H), 2.95 (br,
1 H), 3.99 (m, 1 H), 4.16 (q, J = 7.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 14.2, 14.3, 22.7, 25.6, 29.3, 29.6, 31.9,
36.6, 41.4, 60.8, 68.2, 173.2.
Methyl 3-Hydroxyhexanoate (1)
Yield: 13.14 g (90%, 90 mmol); clear yellow oil.
Methyl 3-Hydroxydodecanoate (7)
IR (film): 3468w, 2957m, 1724s, 1437m, 1166s, 1122m, 993m, 847w
cm–1
.
Yield: 21.62 g (94%, 94 mmol); clear yellow oil.
1H NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 7.3 Hz, 3 H), 1.42 (m, 4 H),
2.38 (dd, J = 9.1, 16.9 Hz, 1 H), 2.49 (dd, J = 4.2, 16.3 Hz, 1 H), 2.90 (br
s, 1 H), 3.69 (s, 3 H), 3.99 (m, 1 H).
IR (film): 3468w, 2923s, 2853m, 1726s, 1437m, 1170s, 732m cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 5.9 Hz, 3 H), 1.28 (m, 16 H),
2.45 (dd, J = 16.2, 18.8 Hz, 1 H), 2.47 (dd, J = 13.2, 16.2 Hz, 1 H), 2.99
(br, 1 H), 3.70 (s, 3 H), 4.00 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 14.0, 18.7, 38.7, 41.2, 51.8, 67.8, 173.5.
13C NMR (75 MHz, CDCl3): δ = 14.1, 22.7, 25.5, 29.3, 29.5, 29.5 29.6,
31.9, 36.6, 41.2, 51.7, 68.0, 173.5.
Ethyl 3-Hydroxyhexanoate (2)
Yield: 14.4 g (90%, 90 mmol); clear yellow oil.
Ethyl 3-Hydroxydodecanoate (8)
IR (film): 3459w, 2960w, 1718s, 1465w, 1372m, 1166s, 1017s, 847w,
733w cm–1
.
Yield: 23.18 g (95%, 95 mmol); clear yellow oil.
1H NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 7.0 Hz, 3 H), 1.25 (t, J = 7.6
Hz, 3 H), 1.41 (m, 4 H), 2.37 (dd, J = 9.1, 16.7 Hz, 1 H), 2.47 (dd, J = 3.4,
17.3 Hz, 1 H), 2.96 (d, J = 3.78 Hz, 1 H), 3.99 (m, 1 H), 4.14 (q, J = 7.0
Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.2, 18.7, 38.7, 41.4, 60.7, 67.8,
173.2.
IR (film): 3496w, 2927m, 1720m, 907s, 728s, 647m cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.87 (t, J = 7.0 Hz, 3 H), 1.26 (m, 19 H),
2.43 (dd, J = 15.9, 19.0 Hz, 1 H), 2.45 (dd, J = 13.5, 16.6 Hz, 1 H), 3.05
(br, 1 H), 3.99 (m, 1 H), 4.16 (q, J = 7.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 14.1, 14.2, 22.7, 25.5, 29.3, 29.5, 29.5,
29.6, 31.9, 36.6, 41.4, 60.6, 68.0, 173.1.
Methyl 3-Hydroxyoctanoate (3)
Saponification of Esters; General Procedure
Yield: 14.79 g (85%, 85 mmol); clear yellow oil.
IR (film): 3458w, 2929m, 1724s, 1437m, 1164s cm–1
1H NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 6.3 Hz, 3 H), 1.29 (m, 8 H),
2.40 (dd, J = 8.8, 16.9 Hz, 1 H), 2.51 (dd, J = 3.8, 15.6 Hz, 1 H), 3.70 (s, 3
H), 3.99 (m, 1 H).
To a 50 mL round-bottomed flask fitted with a stir bar was added
hexane (5 mL) and the respective 3-hydroxymethyl ester (1 mmol).
This mixture was heated to 50 °C at which point sat. KOH in MeOH (0.
5 mL) was added. This led to the instant formation of a precipitate.
The mixture was then stirred vigorously at 60 °C for 30 min, then re-
moved from heat, and the solvents were evaporated under reduced
pressure to provide the product as a potassium salt. This residue was
dissolved in distilled H2O (10 mL) and extracted with CHCl3 (3 × 10
mL). The aqueous layer was collected and acidified with concd HCl to
pH <1. Et2O (20 mL) was added to the aqueous acidic solution and this
solution was stirred vigorously for 1 h. The organic and aqueous lay-
ers were separated the aqueous layer was extracted with Et2O (2 × 20
mL). The combined organic layers were dried (Na2SO4), filtered, and
evaporated under reduced pressure to give the corresponding prod-
uct, which was used without further purification (Table 2).
.
13C NMR (75 MHz, CDCl3): δ = 14.1, 22.7, 25.2, 31.8, 36.6, 41.2, 51.8,
68.1, 173.6.
Ethyl 3-Hydroxyoctanoate (4)
Yield: 16.17 g (86%, 86 mmol); clear yellow oil.
IR (film): 3432w, 2931m, 1718s, 1372m, 1162s, 1026s, 732w cm–1
1H NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 6.7 Hz, 3 H), 1.27 (m, 11 H),
2.39 (dd, J = 8.82, 16.5 Hz, 1 H), 2.50 (dd, J = 3.9, 15.8 Hz, 1 H), 2.90 (s,
1 H), 3.99 (m, 1 H), 4.17 (q, J = 7.0 Hz, 2 H).
.
13C NMR (75 MHz, CDCl3): δ = 14.1, 14.3, 22.7, 25.3, 31.8, 36.6, 41.4,
60.8, 68.2, 173.2.
3-Hydroxyhexanoic Acid (9)
Yield: 95 mg (72%, 0.72 mmol); clear oil.
IR (film): 3390br, 2959m, 1704s, 1407m, 1174m, 1123m, 1017m,
Methyl 3-Hydroxydecanoate (5)
845m cm–1
.
Yield: 18.58 g (92%, 92 mmol); clear yellow oil.
1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 7.30 Hz, 3 H), 1.43 (m, 4 H),
2.43 (dd, J = 8.76, 16.4 Hz, 1 H), 2.53 (dd, J = 4.57, 16.3 Hz, 1 H), 4.03
(m, 1 H), 7.20 (br, 1 H).
IR (film): 3478w, 2925s, 2855m, 1726s, 1437m, 1163s, 1056m, 991s,
723w cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.87 (t, J = 6.5 Hz, 3 H), 1.42 (m, 12 H),
2.40 (dd, J = 8.8, 16.3 Hz, 1 H), 2.51 (dd, J = 3.3, 16.4 Hz, 1 H), 2.84 (br
s, 1 H), 3.71 (s, 3 H), 3.99 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 14.2, 22.7, 25.6, 29.3, 29.6, 31.9, 36.6,
41.2, 51.8, 68.2, 173.6.
13C NMR (75 MHz, CDCl3): δ = 13.9, 18.7, 38.6, 41.2, 68.0, 177.4.
3-Hydroxyoctanoic Acid (10)
Yield: 130 mg (81%, 0.81 mmol); yellow oil.
IR (film): 3312br, 2929m, 1707s, 1374w, 1238m, 1044m, 933w, 872w,
608w cm–1
.
Ethyl 3-Hydroxydecanoate (6)
1H NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 6.76 Hz, 3 H), 1.30 (m, 8 H),
2.46 (dd, J = 9.01, 16.3 Hz, 1 H), 2.56 (dd, J = 4.21, 16.0 Hz, 1 H), 4.03
(m, 1 H), 6.42 (br, 1 H).
Yield: 20.1 g (93%, 93 mmol); clear yellow oil.
IR (film): 3496w, 2927m, 1720m, 907s, 728s, 647m cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 79–82