Ammonium formate → Methyl 2-amino-2-(4-fluorophenyl)acetate

HRID 1977795Notes

Reaction equation

Cl.[CH3:2][O:3][C:4](=[O:21])[CH:5]([NH:13]CC1C=CC=CC=1)[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1.C([O-])=O.[NH4+]>C(O)(C)C.[Pd]>[CH3:2][O:3][C:4](=[O:21])[CH:5]([NH2:13])[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

4-Fluoro-α-[(phenylmethyl)amino]benzeneacetic acid methyl ester hydrochloride (12.2 kg, 39.4 moles) was added to a slurry of 10% palladium-on-carbon (1.2 kg) in isopropanol (50 L). Ammonium formate (5.0 kg, 79.4 moles) was added and the batch was heated to 50° C. Progress of the reaction was monitored by HPLC. The batch was filtered through Hyflo Supercel and the filter cake was washed with isopropanol (25 L). The filtrate was evaporated to low volume and flushed with isopropyl acetate (50 L). The residue was dissolved in isopropyl acetate (30 L) and washed with 5% aqueous potassium phosphate (40 L), followed by saturated aqueous sodium chloride (10 L). The solution was evaporated under vacuum to give 5.79 kg (87% yield) of racemic α-amino-4-fluorobenzeneacetic acid methyl ester.

Workup

filtrationThe batch was filtered through Hyflo Supercel
washthe filter cake was washed with isopropanol (25 L)
customThe filtrate was evaporated to low volume
customflushed with isopropyl acetate (50 L)
dissolutionThe residue was dissolved in isopropyl acetate (30 L)
washwashed with 5% aqueous potassium phosphate (40 L)
customThe solution was evaporated under vacuum

Sources & evidence

ORD record: ord-ee5c746f8a13412daf89c2e2b8d2c5b5
Source dataset: uspto-grants-2001_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06235735B1

Reaction notes

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