o-Fluorobenzaldehyde → 3-(2-Formyl-phenoxy)-3-trifluoromethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1479051Notes

Reaction equation

C(O[K])(C)(C)C.[C:7]([O:11][C:12]([N:14]1[CH2:18][CH2:17][C:16]([OH:23])([C:19]([F:22])([F:21])[F:20])[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].F[C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH:27]=[O:28]>O1CCOCC1.[NH4+].[Cl-]>[C:7]([O:11][C:12]([N:14]1[CH2:18][CH2:17][C:16]([O:23][C:25]2[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=2[CH:27]=[O:28])([C:19]([F:20])([F:21])[F:22])[CH2:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

Conditions

Temperature: 100 °C

Procedure

tBuOK (136 mg; 1.2 mmol; 1.5 eq.) was added at 10° C. to a solution of 3-hydroxy-3-trifluoromethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (247 mg; 0.97 mmol; 1.2 eq.) in 1,4-dioxane (10 mL) and the reaction mixture was stirred at room temperature for 15 minutes whereupon 2-fluoro-benzaldehyde (100 mg; 0.81 mmol; 1 eq.) was added. The reaction mixture was stirred at 100° C. for 3 hours then diluted with sat. aq. NH4Cl and extracted with EA (2×). The combined organics were washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (DCM) afforded the title compound (95 mg, 33%) as a colourless oil. HPLC (max plot) 98.2%, Rt 4.87 min.

Workup

additionwas added
extractionextracted with EA (2×)
washThe combined organics were washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated in vacuo
customPurification by column chromatography (DCM)

Sources & evidence

ORD record: ord-0010df27933d4fd7b4ca58bac7209219
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403835B2

Reaction notes

Loading…