Methanol → HCID 59410118, compound

HRID 1805156Notes

Reaction equation

[F:1][C:2]1([F:23])[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9]([C:16]([F:19])([F:18])[F:17])[CH:8]=2)[C@H:4]([C:20]([OH:22])=[O:21])[CH2:3]1.S(Cl)(Cl)=O.[CH3:28]O>>[F:23][C:2]1([F:1])[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9]([C:16]([F:19])([F:18])[F:17])[CH:8]=2)[C@H:4]([C:20]([O:22][CH3:28])=[O:21])[CH2:3]1

Participants

Reactant 3

HCID 887Methanol

HCID 24386Thionyl Chloride

HCID 59410065HCID 59410065, compound

Product 1

HCID 59410118HCID 59410118, compoundYield 48%

Conditions

Temperature: 0 °C

Procedure

(S)-4,4-difluoro-1-(4-nitro-3-(trifluoromethyl)phenyl)pyrrolidine-2-carboxylic acid (600 mg, 1.76 mmol) was dissolved in methanol (10 mL), cooled to 0° C., and treated dropwise with thionyl chloride (840 mg, 515 μL, 7.08 mmol). The reaction mixture was heated at 50° C. over 48 h. The reaction mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (0-60% ethyl acetate in hexane) to obtain (S)-methyl 4,4-difluoro-1-(4-nitro-3-(trifluoromethyl)phenyl)pyrrolidine-2-carboxylate (300 mg, 48% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.12 (d, J=9.2 Hz, 1H), 7.04 (d, J=2.6 Hz, 1H), 6.97 (dd, J=9.2, 2.7 Hz, 1H), 5.19 (dd, J=9.8, 1.9 Hz, 1H), 4.14-3.99 (m, 2H), 3.69 (s, 3H), 3.11-2.95 (m, 1H), 2.78 (t, J=14.6 Hz, 1H).

Workup

temperatureThe reaction mixture was heated at 50° C. over 48 h
customThe reaction mixture was evaporated in vacuo
customthe residue was purified by silica gel column chromatography (0-60% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-c5420153a679434487d7a095ec2d7c49
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354427B2

Reaction notes

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