Potassium Phosphate, Tribasic → Quinuclidin-3-yl 2-(5-(4-fluorophenyl)thiophen-3-yl)propan-2-ylcarbamate
Reaction equation
Br[C:2]1[S:6][CH:5]=[C:4]([C:7]2([NH:10][C:11](=[O:21])[O:12][CH:13]3[CH:18]4[CH2:19][CH2:20][N:15]([CH2:16][CH2:17]4)[CH2:14]3)[CH2:9][CH2:8]2)[CH:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:22][C:23]1[CH:28]=[CH:27][C:26]([C:2]2[S:6][CH:5]=[C:4]([C:7]([NH:10][C:11](=[O:21])[O:12][CH:13]3[CH:18]4[CH2:17][CH2:16][N:15]([CH2:20][CH2:19]4)[CH2:14]3)([CH3:9])[CH3:8])[CH:3]=2)=[CH:25][CH:24]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
Using general procedure E, quinuclidin-3-yl (1-(5-bromothiophen-3-yl)cyclopropyl)carbamate (0.227 g, 0.742 mmol), 4-fluorophenyl boronic acid (0.208 g, 1.49 mmol), tricyclohexylphosphine (0.021 g, 0.075 mmol), potassium phosphate (0.866, 4.08 mmol) and palladium acetate (8.0 mg, 36 □mol) gave the title compound as a gray solid (0.142 g, 49%). 1H NMR (400 MHz, CDCl3) δ 7.60-7.45 (m, 2H), 7.24-7.19 (m, 1H), 7.10-6.97 (m, 3H), 5.23 (br s, 1H), 4.72-4.61 (m, 1H), 3.30-3.04 (m, 1H), 3.03-2.25 (m, 5H), 2.09-1.02 (m, 11H) ppm. 13C NMR (400 MHz, CDCl3) δ 162.3 (d, J=247.1 Hz), 154.5, 149.8, 143.6, 130.7, 127.4 (d, J=8.1 Hz), 121.8, 118.9, 115.8 (d, J=21.6 Hz), 70.8, 55.5, 53.4, 47.3, 46.4, 29.0, 25.4, 24.4, 19.4 ppm. Purity: 95.8% UPLCMS (210 nm & 254 nm); retention time 0.90 min; (M+1) 389.
Sources & evidence
- ORD record
- ord-ea082c363bad47a088cdb027c4bd9c73
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09139580B2
Reaction notes
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