Ammonium Chloride → (3R,5R)-3-acetyl-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylic acid benzyl ester

HRID 1677091노트

반응식

HRID 1677091 반응식
C(Cl)(=O)C(Cl)=O.[CH2:7]([O:14][C:15]([N:17]1[C@H:22]([C:23]2[CH:28]=[C:27]([F:29])[C:26]([F:30])=[C:25]([F:31])[CH:24]=2)[CH2:21][O:20][CH2:19][C@@H:18]1[C@H:32]([OH:34])[CH3:33])=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Cl-].[NH4+]>C(OCC)(=O)C.C(N(CC)CC)C.O1CCCC1.CS(C)=O>[CH2:7]([O:14][C:15]([N:17]1[C@H:22]([C:23]2[CH:28]=[C:27]([F:29])[C:26]([F:30])=[C:25]([F:31])[CH:24]=2)[CH2:21][O:20][CH2:19][C@@H:18]1[C:32](=[O:34])[CH3:33])=[O:16])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

참가 물질

8

반응물 3

HCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 67373415(3R,5R)-3-((R)-1-hydroxyethyl)-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylic acid benzyl ester

생성물 1

HCID 67372176(3R,5R)-3-acetyl-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylic acid benzyl ester수율 91.4%

시약·촉매·용매 4

HCID 679Dimethyl Sulfoxide용매HCID 8028Tetrahydrofuran용매2회HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

실험 절차

A tetrahydrofuran solution (15 mL) of dimethyl sulfoxide (0.22 mL) was cooled to −78° C., and oxalyl chloride (246 μL) was added dropwise into the resultant solution. The reaction solution was stirred for 5 minutes at the same temperature, and a tetrahydrofuran (5 mL) solution of (3R,5R)-3-((R)-1-hydroxyethyl)-5-(3,4,5-trifluorphenyl)morpholin-4-carboxylic acid benzyl ester (880 mg) was added dropwise. The resultant reaction solution was stirred for 1 hour at the same temperature, and triethylamine (1.54 mL) was added. The reaction solution was returned to room temperature, and stirring was continued for 1 hour. Ammonium chloride aqueous solution and ethyl acetate were added to the reaction solution, and the organic layer was partitioned, and the resultant was dried over anhydrous magnesium sulfate. The solvent was removed under a vacuum, and the resultant was purified by silica gel column chromatography (heptane/ethyl acetate), and the title compound (800 mg) was obtained. The physical property values are as follows.

후처리

  1. customThe resultant reaction solution
  2. additionwas added
  3. customwas returned to room temperature
  4. stirringstirring
  5. waitwas continued for 1 hour
  6. customthe organic layer was partitioned
  7. dry with materialthe resultant was dried over anhydrous magnesium sulfate
  8. customThe solvent was removed under a vacuum
  9. customthe resultant was purified by silica gel column chromatography (heptane/ethyl acetate)

출처 및 근거

ORD 기록
ord-4bd99c254a3a48b6bebc5166a2f22a96
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08008293B2

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