Formic Acid → 3-(3,4-Difluorophenyl)-3-methoxy-1-methylpyrrolidine

HRID 575955Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:9]2([O:14][CH3:15])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[CH:16](O)=O>C=O>[F:1][C:2]1[CH:3]=[C:4]([C:9]2([O:14][CH3:15])[CH2:13][CH2:12][N:11]([CH3:16])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of (−)-3-(3,4-difluorophenyl)-3-methoxypyrrolidine (0.013 g, 0.061 mmol) in formic acid (1 ml) and formaldehyde (37% solution in water, 1 ml) was heated at 85° C. for 5 h. The solution was allowed to reach room temperature. The crude mixture was purified on a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1). The solvent was evaporated. The crude product analyzed by GCMS. Analysis showed 87% conversion. MS m/z (relative intensity, 70 eV) 227 (M+, 5), 212 (26), 197 (30), 141 (47), 57 (bp).

Workup

customto reach room temperature
customThe crude mixture was purified on a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1)
customThe solvent was evaporated

Sources & evidence

ORD record: ord-6231150692704a9db4a31d22d565cfe4
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09035073B2

Reaction notes

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