4-Methylmorpholine → (1R,2S,5R)-tert-butyl 2-((S)-2-(benzyloxycarbonylamino)-4-(methylthio)butanamido)-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylate

HRID 1455331노트

반응식

HRID 1455331 반응식
[NH2:1][C@H:2]1[CH2:8][CH2:7][C@@H:6]2[CH2:9][C@H:3]1[C:4](=[O:17])[N:5]2[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].[C:18]([NH:28][C@H:29]([C:34](O)=[O:35])[CH2:30][CH2:31][S:32][CH3:33])([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[CH2:21]([O:20][C:18]([NH:28][C@@H:29]([CH2:30][CH2:31][S:32][CH3:33])[C:34]([NH:1][C@H:2]1[CH2:8][CH2:7][C@@H:6]2[CH2:9][C@H:3]1[C:4](=[O:17])[N:5]2[C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])=[O:35])=[O:19])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

참가 물질

6

반응물 4

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1550857Benzyloxycarbonyl-L-methionineHCID 68767611(1R,2S,5R)-tert-butyl 2-amino-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylate

생성물 1

HCID 21074905(1R,2S,5R)-tert-butyl 2-((S)-2-(benzyloxycarbonylamino)-4-(methylthio)butanamido)-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylate수율 97%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

Preparation A3, Step 2: A solution of (1R,2S,5R)-tert-butyl 2-amino-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylate (2.5 g) was dissolved in DMF (34 mL) and cooled to 0° C. prior to the addition of N-Cbz methionine (5.3 g), 4-methyl morpholine (3.7 g), and BOP (8.3 g). The reaction was stirred for 12 h at RT and then partitioned between EtOAc and 1N HCl solution. The organic phases were combined, washed with saturated NaHCO3 and brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford (1R,2S,5R)-tert-butyl 2-((S)-2-(benzyloxycarbonylamino)-4-(methylthio)butanamido)-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylate (5.1 g). MS found: (M+H)+=506.2.

후처리

  1. custompartitioned between EtOAc and 1N HCl solution
  2. washwashed with saturated NaHCO3 and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography

출처 및 근거

ORD 기록
ord-a075490855db4b3eaf4262c12e1d7608
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07482335B2

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