Diisopropylethylamine → rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(tetrahydro-pyran-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

HRID 587326노트

반응식

HRID 587326 반응식
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=O)[CH2:3][CH2:2]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[F:41][C:42]1[CH:47]=[CH:46][C:45]([O:48][C:49](=[O:65])[N:50]([C@@H:52]2[C@@H:56]([C:57]3[CH:62]=[CH:61][C:60]([Cl:63])=[C:59]([Cl:64])[CH:58]=3)[CH2:55][NH:54][CH2:53]2)[CH3:51])=[CH:44][CH:43]=1>CN(C=O)C.C(OCC)(=O)C>[F:41][C:42]1[CH:47]=[CH:46][C:45]([O:48][C:49](=[O:65])[N:50]([C@@H:52]2[C@@H:56]([C:57]3[CH:62]=[CH:61][C:60]([Cl:63])=[C:59]([Cl:64])[CH:58]=3)[CH2:55][N:54]([C:7]([CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)=[O:9])[CH2:53]2)[CH3:51])=[CH:44][CH:43]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 219302Oxane-4-carboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67234230rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

생성물 1

HCID 53244483rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(tetrahydro-pyran-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester수율 57%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

실험 절차

To a solution of tetrahydropyran-4-yl-carboxylic acid (51 mg, 0.39 mmol) in DMF (1 mL) was added ambient temperature 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (114 mg, 0.36 mmol) and N,N-diisopropyl ethyl amine (125 mg, 0.97 mmol). After stirring for 15 min at this temperature a solution of rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester (124 mg, 0.32 mol) in DMF (1 mL) was added and stirred for 20 h at ambient temperature. The reaction mixture was diluted with ethyl acetate (10 mL) and washed with aqueous sodium carbonate (1 M, 10 mL), water (10 mL) and brine (10 mL). The aqueous layers were extracted with ethyl acetate (10 mL) and the combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, ethyl acetate:methanol=98:2 to 85:15) afforded the title compound (92 mg, 57%) as a white oil. MS m/e: 495.3 [M]+.

후처리

  1. additionwas added
  2. washwashed with aqueous sodium carbonate (1 M, 10 mL), water (10 mL) and brine (10 mL)
  3. extractionThe aqueous layers were extracted with ethyl acetate (10 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification by chromatography (SiO2, ethyl acetate:methanol=98:2 to 85:15)

출처 및 근거

ORD 기록
ord-a99da81a87ff4ec6be23943e50462189
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09226916B2

반응 노트

불러오는 중…