1-Hydroxybenzotriazole → {(S)-1-cyclohexyl-2-oxo-2-[(S)-2-(3-phenoxy-phenyl)-pyrrolidine-1-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 222504

反応式

HRID 222504 の反応式
[O:1]([C:8]1[CH:9]=[C:10]([C@@H:14]2[CH2:18][CH2:17][CH2:16][NH:15]2)[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:19][C:20]([O:23][C:24]([NH:26][C@H:27]([C:34](O)=[O:35])[CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)=[O:25])([CH3:22])[CH3:21].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.[Cl-].[Na+].O>[C:20]([O:23][C:24](=[O:25])[NH:26][C@@H:27]([CH:28]1[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1)[C:34](=[O:35])[N:15]1[CH2:16][CH2:17][CH2:18][C@H:14]1[C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:9]=1)([CH3:22])([CH3:19])[CH3:21]

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 59787976(S)-2-(3-phenoxy-phenyl)-pyrrolidine

生成物 1

HCID 59787985{(S)-1-cyclohexyl-2-oxo-2-[(S)-2-(3-phenoxy-phenyl)-pyrrolidine-1-yl]-ethyl}-carbamic acid tert-butyl ester収率 68.7%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

(S)-2-(3-phenoxy-phenyl)-pyrrolidine (1.2 g, 5.02 mmol) is added to a solution of Boc-L-α-cyclohexylglycine (1.42 g, 5.2 mmol), HOBt (1.0 g, 7.53 mmol) and HBTU (2.86 g, 7.53 mmol) in 10 mL of DMF. Hunig's base (3.6 Ml, 20 mmol) is added and the mixture is stirred for 30 minutes. The mixture is diluted with brine (20 mL) and extracted with EtOAc (3×10 mL). The organics were combined, dried over Na2SO4, filtered, concentrated under reduced pressures and purified by silica gel column chromatography (20% EtOAc/Hexanes) to give {(S)-1-cyclohexyl-2-oxo-2-[(S)-2-(3-phenoxy-phenyl)-pyrrolidine-1-yl]-ethyl}-carbamic acid tert-butyl ester as a white powder (1.65 g, 66%). LCMS m/z 479.2 (M+1).

後処理

  1. extractionextracted with EtOAc (3×10 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressures
  5. custompurified by silica gel column chromatography (20% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-72d8606d0cc04e7c99c8526d137f18a3
出典データセット
uspto-grants-2012_06
特許番号
US08207183B2

関連ノート

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