Ammonia → (1S,2R,4S,5R)-ethyl 4-amino-1-methylbicyclo[3.1.0]hexane-2-carboxylate

HRID 1854319ノート

反応式

HRID 1854319 の反応式
[CH3:1][C@@:2]12[CH2:7][C@@H:6]1[C:5](=O)[CH2:4][C@@H:3]2[C:9]([O:11][CH2:12][CH3:13])=[O:10].[CH3:14][C@:15]12[CH2:20][C@H:19]1[C:18](=O)[CH2:17][C@H:16]2[C:22]([O:24][CH2:25][CH3:26])=[O:23].[NH3:27].[BH4-].[Na+].[NH4+].[OH-]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[NH2:27][C@H:5]1[C@@H:6]2[C@@:2]([CH3:1])([CH2:7]2)[C@@H:3]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4]1.[NH2:27][C@@H:18]1[C@H:19]2[C@:15]([CH3:14])([CH2:20]2)[C@H:16]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:17]1

参加物

8

反応物 5

HCID 222AmmoniaHCID 14923Ammonium HydroxideHCID 4311764Sodium borohydrideHCID 58009781(1R,2S,5S)-ethyl 1-methyl-4-oxobicyclo[3.1.0]hexane-2-carboxylateHCID 58009803(1S,2R,5R)-ethyl 1-methyl-4-oxobicyclo[3.1.0]hexane-2-carboxylate

生成物 2

HCID 86637177(1R,2S,4R,5S)-ethyl 4-amino-1-methylbicyclo[3.1.0]hexane-2-carboxylateHCID 86637178(1S,2R,4S,5R)-ethyl 4-amino-1-methylbicyclo[3.1.0]hexane-2-carboxylate収率 69%

試薬・触媒・溶媒 1

HCID 11026Titanium isopropoxide触媒

実験手順

To a vial containing (1R,2S,5S)-ethyl 1-methyl-4-oxobicyclo[3.1.0]hexane-2-carboxylate and (1S,2R,5R)-ethyl 1-methyl-4-oxobicyclo[3.1.0]hexane-2-carboxylate (0.305 g, 1.67 mmol) was added a solution of ammonia (2 Nin EtOH) followed by titanium(IV) isopropoxide (0.54 mL, 1.8 mmol). The vial was capped and the reaction was stirred at room temperature overnight. Sodium borohydride (0.095 g, 2.5 mmol) was added and reaction mixture was stirred for about 5 h. Concentrated NH4OH (5 mL) was added and the resulting mixture was stirred for about 5 min. The resulting suspension was filtered and the filter cake was washed with EtOAc (60 mL). The filtrate was partitioned and the aqueous layer was extracted with EtOAc (30 mL). The combined organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated to yield (1R,2S,4R,5S)-ethyl 4-amino-1-methylbicyclo[3.1.0]hexane-2-carboxylate and (1S,2R,4S,5R)-ethyl 4-amino-1-methylbicyclo[3.1.0]hexane-2-carboxylate (0.21 g, 69%). This amine (0.212 g, 1.16 mmol) was reacted with cyclopropanesulfonyl chloride (0.244 g, 1.74 mmol) using General Procedure N to give (1R,2S,4R,5S)-ethyl 4-(cyclopropanesulfonamido)-1-methylbicyclo[3.1.0]hexane-2-carboxylate and (1S,2R,4S,5R)-ethyl 4-(cyclopropanesulfonamido)-1-methylbicyclo[3.1.0]hexane-2-carboxylate (0.11 g, 33%): LC/MS (Table 2, Method a) Rt=2.06 min; MS m/z: 286 (M−H)−.

後処理

  1. customThe vial was capped
  2. customreaction mixture
  3. stirringwas stirred for about 5 h
  4. stirringthe resulting mixture was stirred for about 5 min
  5. filtrationThe resulting suspension was filtered
  6. washthe filter cake was washed with EtOAc (60 mL)
  7. customThe filtrate was partitioned
  8. extractionthe aqueous layer was extracted with EtOAc (30 mL)
  9. washThe combined organic layer was washed with brine
  10. dry with materialdried over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-b8d2682c55f5474aa3683a42e4f201c0
出典データセット
uspto-grants-2015_02
特許番号
US08962629B2

反応ノート

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