Water → tert-butyl (6R,7R)-6-[(3-carbamothioyl-2-oxopyridin-1(2H)-yl)methyl]-7-(4-chloro-3-fluorophenyl)-1,4-oxazepane-4-carboxylate

HRID 1022761Notes

Reaction equation

HRID 1022761 reaction equation
P([O-])(OCC)(SCC)=[S:2].[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C@@H:17]2[O:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19][C@H:18]2[CH2:31][N:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38]#[N:39])[C:33]2=[O:40])=[CH:13][C:12]=1[F:41].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.O>C(OCC)(=O)C.Cl.C(=O)([O-])O.[Na+].C(OCC)(=O)C>[C:38]([C:34]1[C:33](=[O:40])[N:32]([CH2:31][C@H:18]2[C@H:17]([C:14]3[CH:15]=[CH:16][C:11]([Cl:10])=[C:12]([F:41])[CH:13]=3)[O:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:19]2)[CH:37]=[CH:36][CH:35]=1)(=[S:2])[NH2:39]

Participants

8

Reactant 4

HCID 962WaterHCID 90495Di-tert-butyl dicarbonateHCID 53249491DiethyldithiophosphateHCID 66976171HCID 66976171, compound

Product 1

HCID 86663873tert-butyl (6R,7R)-6-[(3-carbamothioyl-2-oxopyridin-1(2H)-yl)methyl]-7-(4-chloro-3-fluorophenyl)-1,4-oxazepane-4-carboxylateYield 60.2%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolventHCID 21866389Hydrogen chloride-ethyl acetateSolvent

Procedure

Diethyl dithiophosphate (0.189 mL, 1.13 mmol) was added to a solution (5 mL, 20.00 mmol) of tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-1,4-oxazepane-4-carboxylate (348 mg, 0.75 mmol) in 4 N hydrogen chloride-ethyl acetate. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was diluted with saturated aqueous sodium hydrogen carbonate solution (10 mL) and ethyl acetate (10 ml), and di-tert-butyl dicarbonate (0.210 mL, 0.90 mmol) was added. The reaction mixture was stirred at room temperature for 4 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (225 mg, 0.454 mmol, 60.2%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionwas added
  3. stirringThe reaction mixture was stirred at room temperature for 4 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-73cf7a0125834b86b2008b92e8493dba
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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