Benzyl Bromide → (1R,3S,5R)-2-Aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-benzyl ester 2-tert-butyl ester

HRID 1052125ノート

反応式

HRID 1052125 の反応式
[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14]([OH:16])=[O:15])[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>O>[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14]([O:16][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:15])[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 11020613(1R,3S,5R)-2-(tert-Butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid

生成物 1

HCID 68283955(1R,3S,5R)-2-Aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-benzyl ester 2-tert-butyl ester

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
0 °C

実験手順

To a solution of (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester (2 g, 8.8 mmol) cooled at 0° C. was added a solution of Cs2CO3 (2.87 g, 8.8 mmol) in water (12.3 mL). After 30 min stirring, the resulting mixture was concentrated and the residue was suspended in DMF (41 mL). The suspension was cooled to 0° C. and benzylbromide (1.045 mL, 8.8 mmol) was added under nitrogen atmosphere. The reaction mixture was stirred at RT for 16 h. DMF was evaporated, the residue was poured in water and extracted with EtOAc (3×50 mL). The combined organic extracts were dried (Phase separator) and concentrated under reduced pressure. The residual oil was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 8:2) to give the title compound. TLC, Rf (c-hexane/EtOAc 8:2)=0.45; MS (UPLC-MS): 318 [M+H]+; tR (HPLC conditions d): 3.89 min.

後処理

  1. concentrationthe resulting mixture was concentrated
  2. stirringThe reaction mixture was stirred at RT for 16 h
  3. customDMF was evaporated
  4. additionthe residue was poured in water
  5. extractionextracted with EtOAc (3×50 mL)
  6. customThe combined organic extracts were dried (Phase separator)
  7. concentrationconcentrated under reduced pressure
  8. customThe residual oil was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 8:2)

出典と根拠

ORDレコード
ord-a2e1216513494642a74de4e4ca5a0343
出典データセット
uspto-grants-2016_07
特許番号
US09388199B2

反応ノート

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