2,6-Difluoro-4-methoxybenzeneboronic acid → 1-Cyclohexyl-3-(3,5-dichloro-2',6'-difluoro-4'-methoxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one
Reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([CH2:14][CH:15]2[CH2:19][CH2:18][N:17]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:16]2=[O:26])=[C:9]([Cl:27])[CH:8]=1)(=O)=O.[F:30][C:31]1[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[C:33]([F:39])[C:32]=1B(O)O>>[CH:20]1([N:17]2[CH2:18][CH2:19][CH:15]([CH2:14][C:10]3[C:11]([Cl:13])=[CH:12][C:7]([C:32]4[C:31]([F:30])=[CH:36][C:35]([O:37][CH3:38])=[CH:34][C:33]=4[F:39])=[CH:8][C:9]=3[Cl:27])[C:16]2=[O:26])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1Participants
Procedure
Using the procedure to synthesize Example 81 and using reagents 3,5-dichloro-4-((1-cyclohexyl-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonate (Example 240) (500 mg, 1.0 mmol) and 2,6-difluoro-4-methoxyphenylboronic acid (590 mg, 3.2 mmol) affords 494 mg (100%) of 1-Cyclohexyl-3-(3,5-dichloro-2′,6′-difluoro-4′-methoxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one. Charge a flask with 1-cyclohexyl-3-(3,5-dichloro-2′,6′-difluoro-4′-methoxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one (500 mg, 1.1 mmol), dissolve in dry methylene chloride (10 mL) and cool to 0° C. under nitrogen. Add BBr3 (0.25 mL, 2.7 mmol) and stir at 0° C. for 1.5 hours. Pour into saturated aqueous sodium bicarbonate and extract with methylene chloride. Dry over sodium sulfate, filter and concentrate in vacuo to yield 470 mg (97%) of the title compound.
Workup
- customto synthesize Example 81
Sources & evidence
- ORD record
- ord-9dc2bcdef9e0442f940751f0f9861098
- Source dataset
- uspto-grants-2010_05
- Patent number
- US07713979B2
Reaction notes
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