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 587326ノート

反応式

HRID 587326 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-a99da81a87ff4ec6be23943e50462189
出典データセット
uspto-grants-2016_01
特許番号
US09226916B2

反応ノート

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