| 47.6% |
Reflux |
Hexadecanedioic acid (4.5 g, 15.71 mmol) was suspended in Toluene (28.1 ml) and the mixture was heated to reflux. 1,1 -di-tert-butoxy-N,Ndimethylmethanamine (10.10 ml, 42.1 mmol) was added drop-wise over 30 mm. Themixture was reflux overnight. The solvent was removed in vacuo at 50°C and the crude material was suspended in CH2C12/EtOAc (75 mL. 1:1) ans stirred for 15 mm. The solids were removed by filtration and washed with CH2C12 (25 mL). The filtration was evaporated in vacuo. The resulting material was suspended in CH2C12 (6 mL), cooled with ice for 10 mins, and filtered. The solvent was removed invacuo to leave crude product which was purified by flash chromatography (silic gel,EtOAc/Hexane) to get 16-(tert-butoxy)-16-oxohexadecanoic acid (2.56 g, 7.47 mmol,47.6 percent yield). Analysis condition D: Retention time = 5.04 mm; ESI-MS(+) m/z269.3 [M — OC(CH3)3]; ‘H NMR (500MHz, METHANOL-d4) ö 2.33 - 2.18 (m, 4H),1.66 - 1.54 (m, 4H), 1.50 - 1.43 (m, 9H), 1.40 - 1.25 (m, 20H). |
| 33% |
Stage #1: at 50℃;
Stage #2: With ethyl acetate In dichloromethane for 0.25 h; |
Hexadecadioic acid (40.0 g, 140 mmol) was suspended in toluene (250 ml) and the mixture was heated to reflux. λ/,λ/-dimethylformamide di-tert-butyl acetal (76.3 g, 375 mmol) was added drop-wise over 4 hours. The mixture was refluxed overnight. The solvent was removed in vacuo at 50 0C, and the crude material was suspended in DCM/AcOEt (500 ml, 1 :1 ) and stirred for 15 mins. The solids were collected by filtration and triturated with DCM (200 ml). The filtrated were evaporated in vacuo to give crude mono-tert-butyl hexadecandioate, 30 grams. This material was suspended in DCM (50 ml), cooled with ice for 10 mins, and filtered. The solvent was removed in vacuo to leave 25 gram crude mono- tert-butyl hexadecandioate, which was recrystallized from heptane (200 ml) to give mono- tert-butyl hexadecandioate, 15.9 g (33 percent).1H-NMR (CDCI3) δ: 2.35 (t, 2H), 2.20 (t, 2H), 1.65-1.55 (m, 4H), 1.44 (s, 9H), 1.34- 1.20 (m, 20 H). |
| 33% |
Reflux |
Hexadecandioic acid (40.0 g, 140 mmol) was suspended in toluene (250 ml) and the mixture was heated toreflux. N,N-Dimethylformamide di-tert-butyl acetal (76.3 g, 375 mmol) was added drop-wise over 4 hours. The mixturewas refluxed overnight. The solvent was removed in vacuo at 50 °C, and the crude material was suspended in dichloromethane/ethyl acetate (500 ml, 1:1) and stirred for 15 mins. The solids were collected by filtration and triturated withdichloromethane (200 ml). The filtrated were evaporated in vacuo to give crude mono-tert-butyl hexadecandioate, 30grams. This material was suspended in dichloromethane (50 ml), cooled with ice for 10 mins, and filtered. The solventwas removed in vacuo to leave 25 gram crude mono-tert-butyl hexadecandioate, which was recrystallized from heptane(200 ml) to give mono-tert-butyl hexadecandioate, 15.9 g (33 percent). Alternatively to recrystallization, the mono-ester canbe purified by silica chromatography with ethyl acetate/heptane. 1H-NMR (CDCl3) δ: 2.35 (t, 2H), 2.20 (t, 2H), 1.65-1.55(m, 4H), 1.44 (s, 9H), 1.34-1.20 (m, 20 H). |
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