Cesium carbonate → Methyl cis(+/-)-5-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-3-methylthiophene-2-carboxylate

HRID 43942Notes

Reaction equation

HRID 43942 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[C:4]([CH3:11])[CH:3]=1.[CH3:12][O:13][C@H:14]1[C@@H:19]([NH:20][C:21](=[O:30])[O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:18][CH2:17][NH:16][CH2:15]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:23]([O:22][C:21]([NH:20][C@H:19]1[CH2:18][CH2:17][N:16]([C:2]2[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[C:4]([CH3:11])[CH:3]=2)[CH2:15][C@H:14]1[O:13][CH3:12])=[O:30])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 53438912Methyl 5-bromo-3-methylthiophene-2-carboxylateHCID 86648490Benzyl cis(+/-)-[3-methoxypiperidin-4-yl]carbamate

Product 1

HCID 86648826Methyl cis(+/-)-5-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-3-methylthiophene-2-carboxylateYield 23.6%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

The same operation as in Example (244b) was performed using methyl 5-bromo-3-methylthiophene-2-carboxylate obtained in Example (245a) (218 mg, 0.93 mmol), benzyl cis(±)-(3-methoxypiperidin-4-yl)-carbamate obtained in Example (40b) (270 mg, 1.02 mmol), palladium acetate (42 mg, 0.19 mmol), BINAP (115 mg, 0.19 mmol) and cesium carbonate (423 mg, 1.30 mmol), to obtain 92 mg of the title compound as a yellow oily substance (24%).

Sources & evidence

ORD record
ord-9f771965f51343cb83a6d86cf4b28fbe
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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