Methyl chloroformate → HCID 15614936, compound

HRID 620347Notes

Reaction equation

HRID 620347 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:18][CH3:19])[C:10]=2[C:14]([F:17])([F:16])[F:15])[C:5]=1[C:20]([NH:22][CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:21].[H][H].Cl[C:34]([O:36][CH3:37])=[O:35]>C1COCC1>[F:3][C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:18][CH3:19])[C:10]=2[C:14]([F:17])([F:16])[F:15])[C:5]=1[C:20]([N:22]([C:34]([O:36][CH3:37])=[O:35])[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:21]

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 24758Sodium hydrideHCID 15614935HCID 15614935, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 15614936HCID 15614936, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (80% dispersion in mineral oil, 1.81 g, 1.1 eq) was added to a stirred, room temperature solution of N-[[2-fluoro-6-methoxy-5-(trifluoromethyl)-1-naphthalenyl]carbonyl]glycine, 1,1-dimethylethyl ester (21.98 g, 54.76 mmol) in dry THF (450 mL) under a dry N2 atmosphere. The suspension was heated in a 50° C. oil bath until hydrogen evolution ceased (approximately 2 hours). The reaction mixture was cooled to 0°-5° C. and a solution of methyl chloroformate (5.76 mL, 1.36 eq) in dry THF (150 mL) was added dropwise over a 20 minute period. The reaction mixture was then warmed to room temperature and stirred for 30 minutes. The reaction mixture was quenched with saturated aqueous NH4Cl and diluted with ether (500 mL). Silica gel (100 mL) was added and the solvents were removed in vacuo. The silica absorbate was flash chromatographed (gradient elution 4:1 to 7:3 petroleum ether:ethyl acetate, silica) to provide the title compound as a white solid (18.79 g, 75%) and starting material (3.07 g, 14%). A small portion was recrystallized from petroleum ether:ether for analysis; m.p. 111°-114° C.

Workup

  1. custom(approximately 2 hours)
  2. temperatureThe reaction mixture was cooled to 0°-5° C.
  3. customThe reaction mixture was quenched with saturated aqueous NH4Cl
  4. additiondiluted with ether (500 mL)
  5. additionSilica gel (100 mL) was added
  6. customthe solvents were removed in vacuo
  7. customchromatographed
  8. wash(gradient elution 4:1 to 7:3 petroleum ether:ethyl acetate, silica)

Sources & evidence

ORD record
ord-f081be6ca040444d85dd561c6147a2de
Source dataset
uspto-grants-1989_04
Patent number
US04820727

Reaction notes

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