Potassium Carbonate → HCID 86605059, compound
Reaction equation
[C:1]1([C@@H:7]2[CH:11]=[C:10](B3OC(C)(C)C(C)(C)O3)[CH2:9][N:8]2[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:28][C:29]1[N:34]=[C:33](Cl)[C:32]([F:36])=[CH:31][N:30]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.Cl[Pd]Cl>[Cl:28][C:29]1[N:34]=[C:33]([C:10]2[CH2:9][N:8]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[C@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:11]=2)[C:32]([F:36])=[CH:31][N:30]=1Participants
Conditions
- Temperature
- 80 °C
Procedure
Crude 34-1 (0.364 g, 0.98 mmol) was dissolved in anhydrous DMF (10 mL), degassed and filled with an N2 atomsphere. 2,4-dichloro-5-fluoropyrimidine (0.25 g, 1.47 mmol), potassium carbonate (0.40 g, 2.94 mmol) and PdCl2 (dppf) (36 mg, 0.05 mmol) were added to the solution and the mixture was stirred at 80° C. for 2.5 h. The reaction mixture was partitioned between water (3×100 mL) and ethyl acetate (100 mL). The organic layer was then washed with sat. aqueous NaCl, dried over sodium sulfate, filtered, and concentrated. The crude oil was purified using reverse phase HPLC (CH3CN/H2O/TFA 0-90% gradient) to provide tert-butyl (2S)-4-(2-chloro-5-fluoropyrimidinyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (34-2). 1H NMR (300 MHz, CDCl3) δ 8.47 (d, J=2.4 Hz, 1H), 7.35 (m, 5H), 6.96 (m, 1H), 5.82 and 5.66 (m, 1H), 4.82 (m, 2H), 1.50 and 1.22 (s, 9H). LRMS: m/z (M-CH3) 361.3 found, 361.3 required.
Workup
- customdegassed
- additionfilled with an N2 atomsphere
- customThe reaction mixture was partitioned between water (3×100 mL) and ethyl acetate (100 mL)
- washThe organic layer was then washed with sat. aqueous NaCl
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe crude oil was purified
Sources & evidence
- ORD record
- ord-5d48c0175f9d444bb1d98408c90cb5d9
- Source dataset
- uspto-grants-2008_03
- Patent number
- US07348440B2
Reaction notes
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