Triethylamine → HCID 118207387, compound

HRID 1507252Notes

Reaction equation

[F:1][C:2]1([F:15])[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][NH:4][CH2:3]1.Br[CH:17]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=2)[C:18]1=[O:33].C(N(CC)CC)C>CN(C=O)C>[F:15][C:2]1([F:1])[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([CH:17]2[CH2:21][CH2:20][N:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:25][CH:24]=3)[C:18]2=[O:33])[CH2:3]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-(3,3-difluoropiperidin-4-yl)phenol (200 mg, 0.94 mmol, E-2a from step D), 3-bromo-1-(4-(trifluoromethyl)benzyl)pyrrolidin-2-one (604 mg, 1.9 mmol), triethylamine (0.65 mL, 4.7 mmol), and 2 mL of DMF was heated in a microwave reactor at 120° C. for 1 h. The cooled reaction mixture was partitioned between water and 30 mL of ethyl acetate, and the aqueous phase was again extracted with 30 mL of ethyl acetate. The combined organic layers were dried over Na2SO4, filtered, and concentrated to afford 150 mg of 3-(3,3-difluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-(trifluoromethyl)-benzyl)pyrrolidin-2-one (0.33 mmol, 35%, 2 diastereoisomers) which was purified and separated in step F. LCMS (method J) RT 0.8 min (60% AP), m/z 455.4 (M+H+).

Workup

customThe cooled reaction mixture
customwas partitioned between water and 30 mL of ethyl acetate
extractionthe aqueous phase was again extracted with 30 mL of ethyl acetate
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-a006e2ea08454a8fb01c998b1f69311c
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221796B2

Reaction notes

Loading…