Hydrochloric Acid → HCID 66880761, compound

HRID 1784044Notes

Reaction equation

HRID 1784044 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])=[CH:4][C:3]=1[F:15].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:26]([O:28][C:29]([CH:31]1[CH:36]2[CH:32]1[C:33](=[O:45])[N:34]([C:38]1[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=1)[C:35]2=[O:37])=[O:30])[CH3:27].Cl>C1COCC1>[CH2:26]([O:28][C:29]([CH:31]1[CH:36]([C:35](=[O:37])[NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]3=[O:14])=[CH:4][C:3]=2[F:15])[CH:32]1[C:33](=[O:45])[NH:34][C:38]1[CH:39]=[CH:40][C:41]([Cl:44])=[CH:42][CH:43]=1)=[O:30])[CH3:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 3120146Ethyl 3-(4-chlorophenyl)-2,4-dioxo-3-azabicyclo[3.1.0]hexane-6-carboxylateHCID 221815481-(4-Amino-3-fluorophenyl)pyridin-2-one

Product 1

HCID 66880761HCID 66880761, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 7 g (34 mmol) of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (prepared according to C. F. Bigge et al., patent application WO 2003045912) in 25 ml of THF was cooled to −78° C. and treated dropwise with 41 ml of a 1M lithium bis(trimethylsilyl)amide-solution in THF and stirred for 30 min. To this solution 9.5 g (32 mmol) of (1RS, 5SR, 6R)-3-(4-chloro-phenyl)-2,4-dioxo-3-aza-bicyclo[3.1.0]hexane-6-carboxylic acid ethyl ester were added portionwise and the mixture was allowed to reach room temperature within a few hours. The mixture was then poured into a diluted aqueous HCl-solution (ca. 0.2 M) and extracted with AcOEt. The combined organic phases were dried with Na2SO4. Evaporation of the solvent and chromatography on silica gel with dichloromethane and then with a gradient of dichloromethane/MeOH from 98:2 to 95:5 gave 4.1 g (24%) of the title compound. Light brown solid. MS: 496 (M−H)−.

Workup

  1. waitto reach room temperature within a few hours
  2. extractionextracted with AcOEt
  3. dry with materialThe combined organic phases were dried with Na2SO4
  4. customEvaporation of the solvent and chromatography on silica gel with dichloromethane

Sources & evidence

ORD record
ord-f0500249342f437da4972a50b3c26b60
Source dataset
uspto-grants-2009_03
Patent number
US07501413B2

Reaction notes

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