Cesium carbonate → Ethyl 5-(4-methyl-1,4-diazepan-1-yl)thiophene-2-carboxylate

HRID 1092115Notes

Reaction equation

Br[C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=1.[CH3:12][N:13]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15][CH2:14]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+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:12][N:13]1[CH2:19][CH2:18][CH2:17][N:16]([C:2]2[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=2)[CH2:15][CH2:14]1

Participants

Conditions

Temperature: 80 °C

Procedure

Palladium(II)acetate (0.135 g, 0.60 mmol) was added to ethyl 5-bromothiophene-2-carboxylate (1.411 g, 6 mmol), 1-methyl-1,4-diazepane (0.822 g, 7.20 mmol), BINAP (0.374 g, 0.60 mmol) and cesium carbonate (2.74 g, 8.40 mmol) in dioxane (40 mL) warmed to 80° C. for 18 h under nitrogen. The crude reaction mixture was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 7M NH3/MeOH. Fractions were evaporated to dryness to afford the crude product. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 5% 3M ammonia/MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 5-(4-methyl-1,4-diazepan-1-yl)thiophene-2-carboxylate (0.204 g, 12.67%) as a yellow gum.

Workup

customThe crude reaction mixture
customwas purified by ion exchange chromatography
washThe desired product was eluted from the column
customFractions were evaporated to dryness
customto afford the crude product
customThe crude product was purified by silica column chromatography
washeluting with a gradient of 0 to 5% 3M ammonia/MeOH in DCM
customPure fractions were evaporated to dryness

Sources & evidence

ORD record: ord-cce7dcfe6cfc49e280e1449cb0b0dea7
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129391B2

Reaction notes

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