Hydrochloric Acid → HCID 66882355, compound

HRID 1784048Notes

Reaction equation

HRID 1784048 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[CH2:33][O:34][C:35]2=[O:37])=[O:30])[CH3:27].Cl>C1COCC1>[CH2:26]([O:28][C:29]([CH:31]1[CH:36]([CH2:35][OH:37])[CH:32]1[C:33](=[O:34])[NH: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])=[O:30])[CH3:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 221815481-(4-Amino-3-fluorophenyl)pyridin-2-oneHCID 66882562HCID 66882562, compound

Product 1

HCID 66882355HCID 66882355, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 600 mg (2.9 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 10 ml of THF was cooled to −78° C. and treated dropwise with 3.2 ml of a 1M lithium bis(trimethylsilyl)amide-solution in THF and stirred for 30 min. To this solution 500 mg (3.2 mmol) of (1SR,5SR,6SR) 2-oxo-3-oxa-bicyclo[3.1.0]hexane-6-carboxylic acid ethyl ester dissolved in 5m of THF were added portionwise. The mixture was allowed to reach RT and stirred for 10 hrs. 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. Filtration, evaporation of the solvent gave 630 mg (57%) of (1SR,2SR,3RS) 2-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-3-hydroxymethyl-cyclopropanecarboxylic acid ethyl ester. Orange foam. MS: 373 (M−H)−.

Workup

  1. additionwere added portionwise
  2. customto reach RT
  3. stirringstirred for 10 hrs
  4. extractionextracted with AcOEt
  5. dry with materialThe combined organic phases were dried with Na2SO4
  6. filtrationFiltration, evaporation of the solvent

Sources & evidence

ORD record
ord-94141face69b4a28a8869761c8e6b73a
Source dataset
uspto-grants-2009_03
Patent number
US07501413B2

Reaction notes

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