Cesium carbonate → 2-Bromo-4-fluoro-6-(1-oxo-3,4,5,6,7,8-hexahydrobenzothieno[2,3-c]pyridin-2(1H)-yl)benzyl Acetate

HRID 1024020Notes

Reaction equation

HRID 1024020 reaction equation
[C:1]1(=[O:14])[C:6]2[S:7][C:8]3[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=3[C:5]=2[CH2:4][CH2:3][NH:2]1.[C:15]([O:18][CH2:19][C:20]1[C:25]([Br:26])=[CH:24][C:23]([F:27])=[CH:22][C:21]=1Br)(=[O:17])[CH3:16].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:15]([O:18][CH2:19][C:20]1[C:21]([N:2]2[CH2:3][CH2:4][C:5]3[C:9]4[CH2:10][CH2:11][CH2:12][CH2:13][C:8]=4[S:7][C:6]=3[C:1]2=[O:14])=[CH:22][C:23]([F:27])=[CH:24][C:25]=1[Br:26])(=[O:17])[CH3:16]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 208997543,4,5,6,7,8-Hexahydrobenzo[4,5]thieno[2,3-c]pyridin-1(2H)-oneHCID 670165932,6-Dibromo-4-fluorobenzyl acetate

Product 1

HCID 580437562-Bromo-4-fluoro-6-(1-oxo-3,4,5,6,7,8-hexahydrobenzothieno[2,3-c]pyridin-2(1H)-yl)benzyl AcetateYield 77%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 103e (3 g, 14.5 mmol), 2,6-dibromo-4-fluorobenzyl acetate 101j (14 g, 43.5 mmol), Xantphos (839 mg, 1.45 mmol), Pd2(dba)3 (1.33 g, 1.45 mmol) and Cs2CO3 (9.4 g, 29 mmol) in dioxane (200 mL) was heated at 100° for 15 h under nitrogen. After filtration, the filtrate was evaporated in vacuo and purified by flash column eluting with ethyl acetate/petroleum ether (1:1) to give 103f (5 g, yield 77%) as a yellow solid. LCMS: (M+H)+452. 1H NMR (500 MHz, DMSO) δ 7.71 (dd, J=2.5, 1H), 7.51 (dd, J=3, 1H), 5.04 (m, 1H), 4.10 (m, 1H), 3.68 (m, 1H), 2.86 (m, 2H), 2.77 (m, 2H), 2.55 (m, 3H), 1.98 (s, 3H), 1.78 (m, 4H)

Workup

  1. filtrationAfter filtration
  2. customthe filtrate was evaporated in vacuo
  3. custompurified by flash column
  4. washeluting with ethyl acetate/petroleum ether (1:1)

Sources & evidence

ORD record
ord-be75f7e7887341f9b6af103142e16415
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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