J. H. Horner and M. Newcomb
22.4 (CH2), 24.7 (CH2), 28.3 (pentet, J= 19Hz, CD2), 29.1 (CH2), 29.2 (CH2), 29.3 Methylene chloride (200mL) was added, and the solution was washed with
(CH2), 29.4 (CH2), 29.5 (CH2), 30.8 (pentet J = 19 Hz, CD2) 33.9 (CH2), 180.2 (NaHCO3, aq) and brine. The organic layer was dried over MgSO4 and
(COOH). Mass spectrum: m/z (intensity), 204 M+ (31), 175 (12), 161 filtered. The solvent was removed by rotary evaporation to give 8b as a
(38), 129 (45), 87 (85), 73 (100); HRMS (EI), calcd for C12H20D4O2 (M+): clear oil (0.37 g, 92% yield) that was used without further purification to
204.20274; found: 204.20161.
prepare 9b. 1H NMR: d 0.87 (t, J = 7.4 Hz, 3H), 1.20–1.38 (m, 22H),
1.56 (pentet, J = 7.4 Hz, 3H), 3.63 (t, J = 6.6 Hz, 2H). 13C NMR: d 14.1 (CH3),
22.4 (CH2), 25.7 (CH2), 28.2 (pentet, J = 19 Hz, CD2), 29.4 (CH2), 29.61
(CH2), 29.62 (CH2), 29.67 (CH2), 29.69 (CH2), 29.70 (CH2), 29.71 (CH2),
30.9 (pentet, J = 19 Hz, CD2), 32.8 CH2), 63.1 (CH2). Mass spectrum:
m/z (intensity), 245 (M À 1)+ (3.6), 228 (27), 200 (20), 111 (100). HRMS
(EI), calcd for C16H34D4O (M À 1): 245.27825; found: 245.27759.
Methyl 9,9,10,10-tetradeuteriododecanoate (10a)
Acid 9a (0.020 g, 0.0001 mol) was dissolved in diethyl ether (50 mL). An
ethereal solution of diazomethane (1 mL) was added, and the resulting
yellow solution was allowed to stand at room temperature for 15 h.
Solvent removal by rotary evaporation gave an oil (0.021 g, 100%).
1H NMR: d 0.86 (t, J = 7.4 Hz, 3H), 1.20–1.35 (m, 12H), 1.61 (m, 2H),
2.29 (t, J = 7.5Hz, 2H), 3.66 (s, 3H). 13C NMR: d 14.0 (CH3), 22.4 (CH2),
25.0 (CH2), 28.2 (pentet, J= 19 Hz, CD2), 29.1 (CH2), 29.3 (CH2), 29.4
(CH2), 29.5 (CH2), 29.6 (CH2), 30.7 (pentet J= 19 Hz, CD2), 34.1 (CH2),
51.4 (CH3), 174.3 (C). Mass spectrum: m/z (intensity), 218 M+ (5.5), 187
(10), 175 (13), 143 (16), 87 (66), 74 (100). HRMS (EI), calcd for C13H22D4O2
(M+): 218.21839; found: 218.21930.
13,13,14,14-Tetradeuteriohexadecanoic acid (9b)
Alcohol 8b (0.24 g, 0.001 mol) was dissolved in anhydrous DMF (6 mL).
Pyridinium dichromate (1.9 g, 0.005 mol) was added, and the mixture
was stirred under N2 for 3 days. The reaction mixture was poured into
water (50 mL), and the mixture was extracted with hexane (3 Â 40 mL).
The combined hexane layer was washed with brine and dried over
MgSO4. After filtration, solvent was removed by rotary evaporation. The
resulting solid was chromatographed on silica gel (10:1 hexanes–ethyl
acetate) to give a white solid (0.14 g, 54%, m.p. 60–61 ꢀC). 1H NMR: d 0.87
(t, J = 7.6 Hz, 3H), 1.20–1.40 (m, 20H), 1.61 (pentet, J = 7.2 Hz, 2H),
2.34 (t, J = 7.5 Hz, 2H). 13C NMR: d 14.0 (CH3), 22.5 (CH2), 24.7 (CH2),
28.3 (pentet, J = 19Hz, CD2), 29.1 (CH2), 29.3 (CH2), 29.41 (CH2), 29.44
(CH2), 29.60 (CH2), 29.65 (CH2), 29.68(CH2), 29.70 (CH2) 30.9 (pentet
J = 19 Hz, CD2), 34.1 (CH2), 180.5 (COOH). HRMS (EI), calcd for C16H28D4O2
(M+): 260.26534; found: 260.26617.
2-(13,13,14,14-Tetradeuteriohexadec-8-ynyl-1-oxy)tetrahydropyran
(6b)
THP ether 14b (1.0 g, 0.0045 mol) was dissolved in THF (15 mL) under N2,
and the mixture was cooled to 0 ꢀC in an ice bath. BuLi (3.3 mL, 1.6 M in
hexane, 0.0052 mol) was added, and the mixture was stirred for 30 min.
Tosylate 5 (0.95 g, 0.0034 mol) and NaI (0.15 g) were added, and the
mixture was heated at reflux for 20 h. The reaction mixture was poured
into hexane (200 mL), and the mixture was filtered through a pad of silica
gel. The silica gel was washed with 10:1 hexanes–ethyl acetate. Solvent
was removed from the filtrate by rotary evaporation, and the resulting
oil was chromatographed on silica (5:1 hexanes–ethyl acetate) to give
6b as a clear oil (1.05 g, 95%). 1H NMR d 0.84 (t, J = 7.4 Hz, 3H),
1.20–1.38 (m, 10H), 1.40–1.60 (m, 10H), 1.67 (m, 1H), 1.80 (m, 1H),
2.10 (t, J = 5.5 Hz, 2H), 3.33 (m, 1H), 3.46 (m, 1H), 3.69 (m, 1H), 3.83
(m, 1H), 4.54 (br s, 1H). 13C NMR d 13.9 (CH3), 18.62 (CH2), 18.64 (CH2),
19.5 (CH2), 22.2 (CH2), 25.4 (CH2), 26.1 (CH2), 27.7 (pentet, J = 19 Hz,
CD2), 28.3 (CH2), 28.6 (CH2), 28.9 (CH2), 29.02 (CH2), 29.05 (CH2), 29.6
(CH2), 30.7 (CH2), 30.7 (pentet, J= 19 Hz, CD2), 61.9 (CH2), 67.4 (CH2),
79.9 (C), 80.0 (C), 98.6 (CH). Mass spectrum: m/z (intensity), 326 M+
(0.006), 325 (.006), 101(15), 85(100). HRMS (EI), calcd for C21H34D4O2
(M+): 326.31229; found: 326.31143.
Methyl 13,13,14,14-tetradeuteriohexadecanoate (10b)
Acid 9b (0.025 g, 0.0001 mol) was dissolved in diethyl ether (10 mL). An
ethereal solution of diazomethane was added, and the resulting yellow
solution was allowed to stand at room temperature for 2 h. Solvent
removal by rotary evaporation gave an oil (0.023 g, 88%). 1H NMR:
d 0.87 (t, J = 7.4 Hz, 3H), 1.27 (m, 20H), 1.61 (pentet, J = 7.1 Hz, 2H), 2.30
(t, J = 7.5 Hz, 2H), 3.66 (s, 3H). 13C NMR: d 14.1 (CH3), 22.4 (CH2), 25.0
(CH2), 29.2 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 29.6 (CH2), 29.65
(CH2), 29.68 (CH2), 29.7 (CH2), 34.1 (CH2), 51.4 (CH3), 174.3 (C). Mass
spectrum: m/z (intensity), 274 M+ (100), 231 (31), 143 (56). HRMS (EI),
calcd for C17H30D4O2 (M+): 274.28099; found: 274.28197.
2-(Non-2-ynyl-1-oxy)tetrahydropyran (12)
2-(13,13,14,14-Tetradeuteriohexadecyl-1-oxy)tetrahydropyran (7b)
THP ether 11 (7.0 g, 0.05 mol) was dissolved in THF (50 mL), and the
mixture was cooled in an ice bath under a nitrogen atmosphere. BuLi
(37 mL, 1.6 M, 0.06 mol) was added slowly by syringe. 1-Iodohexane
(15.5 g, 0.07 mol) was added, and the mixture was heated at reflux for
15 h. The reaction mixture was poured into hexane (200 mL), and the
resulting solution was filtered through silica gel. The solvent was
removed by rotary evaporation, and the resulting oil was chromato-
graphed on silica gel (hexane to 10:1 hexanes–ethyl acetate) to give
Wilkinson’s catalyst (0.18 g) was added to dry benzene (20 mL). Nitrogen
was passed over the vigorously stirred solution for 10 min. Hydrogen gas
was passed slowly through the solution for approximately 15 min until
the solution turned from dark red to orange. A gas buret was charged
with hydrogen and attached to the flask. THP ether 6b (0.75 g,
0.0023 mol) was added. Small aliquots were periodically removed and
analyzed by GC to monitor reaction progress. After 15 h, the reaction
mixture was poured into 10:1 hexane–ethyl acetate, and the solution
was filtered through silica gel. After solvent removal, the resulting oil
was chromatographed on silica gel (20:1 hexanes–ethyl acetate) to give
7b (0.65 g, 86%) as an oil. 1H NMR d 0.85 (t, J = 7.4 Hz, 3H), 1.20–1.36
(m, 22H), 1.45–1.60 (m, 6H), 1.68 (m, 1H), 1.81 (m, 1H), 3.34 (dt, J = 9.5,
6.7 Hz, 1H), 3.46 (m, 1H), 3.71 (dt, J = 9.5, 6.9 Hz, 1H), 3.85 (m, 1H),
4.55 (t, J = 3.5 Hz, 1H). 13C NMR: d 14.0 (CH3), 19.7 (CH2), 22.4 (CH2),
25.8 (CH2), 26.3 (CH2), 28.3 (pentet, J = 19 Hz, CD2), 29.4 (CH2), 29.5
(CH2), 29.61 (CH2), 29.62 (CH2), 29.67 (CH2), 29.68 (CH2), 29.70 (CH2),
29.8 (CH2), 30.7 (CH2), 30.8 (pentet, J= 19 Hz, CD2), 62.2 (CH2), 67.6
(CH2), 98.8 (CH). Mass spectrum: m/z (intensity), 330 M+ (0.1), 329 (0.4),
257 (0.5), 115 (3); 101(8), 85 (100). HRMS (EI), calcd for C21H38D4O2
(M+), 330.34359; found: 330.34256.
1
12 (8.1g, 72%) as an oil. H NMR: d 0.84 (m, 3H), 1.42–1.56 (m, 4H), 1.24
(m, 4H), 1.34 (m, 2H), 1.48 (m, 4H), 1.58 (m, 2H), 1.68 (m, 1H), 1.80 (m, 1H),
2.17 (m, 2H), 3.48 (m, 1H), 3.80 (m, 1H), 4.17 (m, 1H), 4.25 (m, 1H), 4.78
(m, 1H). 13C NMR: d 14.0 (CH3), 18.8 (CH2), 19.1 (CH2), 22.5 (CH2),
25.4 (CH2), 28.5 (CH2), 28.6 (CH2), 30.3 (CH2), 31.3 (CH2), 54.6 (CH2),
61.9 (CH2), 75.2 (C), 86.6 (C), 96.6 (CH).
2-Nonyn-1-ol (13)
THP ether 12 (4.5 g, 0.02 mol) was dissolved in methanol (50 mL), and the
mixture was cooled in an ice bath. p-Toluenesulfonic acid (0.5 g) was
added, and the mixture was stirred for 16 h at room temperature. Water
(200 mL) was added, and the mixture was extracted with methylene
chloride. The organic extract was washed with brine and dried over
MgSO4. Solvent was removed by rotary evaporation, and the resulting
oil was chromatographed on silica gel (10:1 hexanes–ethyl acetate) to
13,13,14,14-Tetradeuteriohexadecan-1-ol (8b)
THP ether 7b (0.53 g, 0.0016 mol) was dissolved in methanol (30 mL), and give 13 as a clear oil (2.2 g, 79%). 1H NMR: d 0.83 (t, J = 7.2 Hz, 3H),
the mixture was cooled in an ice bath. p-Toluenesulfonic acid (0.1 g) was 1.16–1.27 (m, 4H), 1.28–1.35 (m, 2H), 1.43 (pentet, J = 7.3 Hz, 2H),
added, and the mixture was stirred for 16 h at room temperature. 2.14 (t, J = 7.1 Hz, 2H), 2.81 (t, J = 5.3 Hz, 1H), 4.17 (m, 2H). 13C NMR:
Copyright © 2012 John Wiley & Sons, Ltd.
J. Label Compd. Radiopharm 2012