144-33-2 → HCID 130272602, compound

HRID 1486667Notes

Reaction equation

HRID 1486667 reaction equation
[F:1][C@H:2]1[CH2:7][C@@H:6]2[C@@H:4]([C@H:5]2[C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:3]1=O.C[Si]([C:18]#[N:19])(C)C.C([O-])(=O)CC(CC([O-])=O)(C(O)=O)O.[Na+].[Na+].[NH3:35].CO>CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4]>[NH2:35][C@@:3]1([C:18]#[N:19])[C@@H:2]([F:1])[CH2:7][C@@H:6]2[C@H:4]1[C@H:5]2[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

6

Reactant 4

HCID 8950144-33-2HCID 82115Trimethylsilyl cyanideHCID 10773886HCID 10773886, compoundHCID 21705897Ammonia methanol

Product 1

HCID 130272602HCID 130272602, compound

Reagents, catalysts & solvents 1

HCID 11026Titanium isopropoxideCatalyst

Procedure

To a solution of (1S,3S,5R,6S)-ethyl 3-fluoro-2-oxobicyclo[3.1.0]hexane-6-carboxylate (WO 2000/37410 pamphlet, 37.17 g) in 8 mol/L ammonia-methanol (250 mL), tetraisopropyl orthotitanate (68.09 g) and trimethylsilyl cyanide (23.03 g) were added dropwise sequentially while cooling on ice. The mixture was stirred on ice for 3.5 hours and then a 12.4% aqueous disodium citrate solution (848 g) was added dropwise to the reaction solution. The mixture was extracted twice with toluene (743 ml) and then the combined organic layer was dried over anhydrous sodium sulfate. The insoluble was collected by filtration and then washed with toluene (186 mL), and the solution containing (1S,2S,3S,5R,6S)-ethyl 2-amino-2-cyano-3-fluorobicyclo[3.1.0]hexane-6-carboxylate (Reference Example 2-1) was used for the next reaction without concentration and purification of the filtrate.

Workup

  1. temperaturewhile cooling on ice
  2. extractionThe mixture was extracted twice with toluene (743 ml)
  3. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
  4. filtrationThe insoluble was collected by filtration
  5. washwashed with toluene (186 mL)
  6. additionthe solution containing (1S,2S,3S,5R,6S)-ethyl 2-amino-2-cyano-3-fluorobicyclo[3.1.0]hexane-6-carboxylate (Reference Example 2-1)
  7. customwas used for the next reaction without concentration and purification of the filtrate

Sources & evidence

ORD record
ord-5030608e498142cab37019a4290cef5e
Source dataset
uspto-grants-2016_08
Patent number
US09428483B2

Reaction notes

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