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

HRID 2204468Notes

Reaction equation

HRID 2204468 reaction equation
[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

Participants

8

Reactant 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

Product 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-carboxylateYield 69%

Reagents, catalysts & solvents 1

HCID 11026Titanium isopropoxideCatalyst

Procedure

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)−.

Workup

  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

Sources & evidence

ORD record
ord-cf66a67e8d2d4babab8935ba3d38d165
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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