Methyl chloroformate → N-[[6-Methoxy-2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)-1-naphthalenyl]carbonyl]-N-(methoxycarbonyl)glycine, 1,1-Dimethylethyl Ester

HRID 620359Notes

Reaction equation

HRID 620359 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[C:6]([C:32]([F:35])([F:34])[F:33])=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([C:15]([NH:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:16])=[C:10]([O:26][CH2:27][C:28]([F:31])([F:30])[F:29])[CH:9]=[CH:8]2.Cl[C:37]([O:39][CH3:40])=[O:38]>C1COCC1>[CH3:3][O:4][C:5]1[C:6]([C:32]([F:33])([F:34])[F:35])=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([C:15]([N:17]([C:37]([O:39][CH3:40])=[O:38])[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])=[O:16])=[C:10]([O:26][CH2:27][C:28]([F:29])([F:30])[F:31])[CH:9]=[CH:8]2

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 24758Sodium hydrideHCID 15614967N-[[6-Methoxy-2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)-1-naphthalenyl]carbonyl]glycine, 1,1-Dimethylethyl Ester

Product 1

HCID 15614946N-[[6-Methoxy-2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)-1-naphthalenyl]carbonyl]-N-(methoxycarbonyl)glycine, 1,1-Dimethylethyl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

Sodium hydride (80% by weight dispersion in mineral oil, 381 mg, 1.1 eq) was added to a stirred solution of N-[[6-methoxy-2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)-1-naphthalenyl]carbonyl]glycine, 1,1-dimethylethyl ester (5.56 g, 11.5 mmol) in anhydrous THF (90 mL) at room temperature under a dry nitrogen atmosphere. The reaction was heated at 55° C. for 2 hours, then cooled to 0° C. in an ice bath. A solution of methyl chloroformate (1.21 mL, 1.36 eq) in anhydrous THF (30 mL) was slowly added to the 0° C. reaction mixture over 25 minutes. After 10 minutes, the reaction was warmed to room temperature. After 1 hour, the reaction was quenched with saturated aqueous ammonium chloride (1 mL), diluted with ether (100 mL) and preabsorbed onto silica gel. The product was flash chromatographed (4:1 petroleum ether:ethyl acetate, silica) to provide the title compound as white flakes (4.42 g, 71%), m.p. 53°-54° C.

Workup

  1. temperaturecooled to 0° C. in an ice bath
  2. temperaturethe reaction was warmed to room temperature
  3. waitAfter 1 hour
  4. customthe reaction was quenched with saturated aqueous ammonium chloride (1 mL)
  5. additiondiluted with ether (100 mL)
  6. custompreabsorbed onto silica gel
  7. customchromatographed (4:1 petroleum ether:ethyl acetate, silica)

Sources & evidence

ORD record
ord-800996bb71624ec8a2c3cdaac751f65a
Source dataset
uspto-grants-1989_04
Patent number
US04820727

Reaction notes

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