Triethylamine → 3-[(4S,5S)-3-benzyloxycarbonyl-4-isobutyl-2,2-dimethyloxazolidin-5-yl]-2-[2-(2-tetrahydropyranyloxy)ethyl]-2-propenoic acid methylamide

HRID 232135Notes

Reaction equation

HRID 232135 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C@@H:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[C@H:14]([CH:20]=[C:21]([CH2:25][CH2:26][O:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][O:29]2)[C:22](O)=[O:23])[O:13][C:12]1([CH3:35])[CH3:34])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[NH-].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[CH2:55]([N:57](CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[CH3:55][NH:57][C:22](=[O:23])[C:21]([CH2:25][CH2:26][O:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][O:29]1)=[CH:20][C@@H:14]1[O:13][C:12]([CH3:35])([CH3:34])[N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[C@H:15]1[CH2:16][CH:17]([CH3:19])[CH3:18]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 21952893MethylamideHCID 700453933-[(4S,5S)-3-benzyloxycarbonyl-4-isobutyl-2,2-dimethyloxazolidin-5-yl]-2-[2-(2-tetrahydropyranyloxy)ethyl]-2-propenoic acid

Product 1

HCID 700461233-[(4S,5S)-3-benzyloxycarbonyl-4-isobutyl-2,2-dimethyloxazolidin-5-yl]-2-[2-(2-tetrahydropyranyloxy)ethyl]-2-propenoic acid methylamideYield 37.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

45 mg of 3-[(4S,5S)-3-benzyloxycarbonyl-4-isobutyl-2,2-dimethyloxazolidin-5-yl]-2-[2-(2-tetrahydropyranyloxy)ethyl]-2-propenoic acid was dissolved in 0.3 ml of dry dimethylformamide, and 3.71 mg of methylamide, 32.9 mg of diphenylphosphorylazide and 12.1 mg of triethylamine were added thereto at -10° C. under stirring. Then, the mixture was stirred at -10° C. for one hour and at room temperature overnight. To the reaction solution, 20 ml of ethyl acetate was added. The ethyl acetate layer was washed sequentially with a 10% citric acid aqueous solution, water, a 4% sodium hydrogencarbonate aqueous solution, water and a saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (Kieselgel 60) by using a mixture of chloroform/methanol (5/1) to obtain 17.5 mg of 3-[(4S,5S)-3-benzyloxycarbonyl-4-isobutyl- 2,2-dimethyloxazolidin-5-yl]-2-[2-(2-tetrahydropyranyloxy)ethyl]-2-propenoic acid methylamide as a colorless oily substance.

Workup

  1. stirringThen, the mixture was stirred at -10° C. for one hour and at room temperature overnight
  2. washThe ethyl acetate layer was washed sequentially with a 10% citric acid aqueous solution, water
  3. dry with materiala 4% sodium hydrogencarbonate aqueous solution, water and a saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (Kieselgel 60)
  6. additiona mixture of chloroform/methanol (5/1)

Sources & evidence

ORD record
ord-2d56b564609d42d08e1c9d60d1377761
Source dataset
uspto-grants-1989_07
Patent number
US04851387

Reaction notes

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