Formaldehyde → HCID 57986840, compound

HRID 871923Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([F:19])([C:14]2[S:15][CH:16]=[CH:17][N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[CH2:25]=[O:26]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([F:19])([C:14]2[S:15][C:16]([CH2:25][OH:26])=[CH:17][N:18]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: -78 °C

Procedure

To a cooled (−78° C.) and stirred solution of 4-fluoro-4-thiazol-2-yl-piperidine-1-carboxylic acid tert-butyl ester (3.65 g, 12.7 mmol) in THF (20 mL) was added n-BuLi (1.33 mL, 1.05 eq., 10.0 M in hexanes). The mixture was stirred at this temperature for 30 minutes. Then a suspension of paraformaldehyde (383 mg, 1 eq.) in THF (10 mL) was added in. The resulting mixture was continued to stir at −78° C. for another 30 minutes and gradually warmed to room temperature overnight. The reaction was quenched by addition of water (10 mL). The mixture was extracted with EtOAc. The organic phase was washed with brine and dried over Na2SO4. After removal of the solvent, the crude product was purified on silica gel (60% EtOAc in hexanes) to afford the desired product as a pale yellow solid.

Workup

additionwas added in
stirringto stir at −78° C. for another 30 minutes
temperaturegradually warmed to room temperature overnight
customThe reaction was quenched by addition of water (10 mL)
extractionThe mixture was extracted with EtOAc
washThe organic phase was washed with brine
dry with materialdried over Na2SO4
customAfter removal of the solvent
customthe crude product was purified on silica gel (60% EtOAc in hexanes)

Sources & evidence

ORD record: ord-703ca36a7c0c46739763d0e546f8c1eb
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08975258B2

Reaction notes

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