Allyl bromide → Methyl 6-allyl-2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate

HRID 1615555Notes

Reaction equation

HRID 1615555 reaction equation
[Br:1][C:2]1[S:23][C:5]2[C:6](=[O:22])[NH:7][CH:8]([C:18]([O:20][CH3:21])=[O:19])[CH:9]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=3)[C:4]=2[CH:3]=1.O1C[CH2:27][CH2:26][CH2:25]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C(Br)C=C>>[CH2:27]([N:7]1[CH:8]([C:18]([O:20][CH3:21])=[O:19])[CH:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=2)[C:4]2[CH:3]=[C:2]([Br:1])[S:23][C:5]=2[C:6]1=[O:22])[CH:26]=[CH2:25]

Participants

5

Reactant 4

HCID 7841Allyl bromideHCID 8028Tetrahydrofuran2×HCID 2733832Lithium HexamethyldisilazideHCID 68183119Methyl 2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate

Product 1

HCID 68183088Methyl 6-allyl-2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate

Procedure

To a solution of methyl 2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate (0.320 g, 0.735 mmol) in tetrahydrofuran (19 mL, 230 mmol) was added lithium bis(trimethylsilyl)amide (1.103 mmol, 1.103 mmol) in tetrahydrofuran (0.956 mL, 11.8 mmol) at −78° C. under argon. The mixture was stirred for 30 min before allyl bromide (1.27 mL, 14.7 mmol) was added. The reaction mixture was warmed to rt and stirred for 3 hr. The mixture was quenched by addition of sat. NH4Cl and then extracted with EtOAc. The organic layer was separated, dried, and concentrated in vacuo. The residue was purified by silica gel chromatography to afford methyl 6-allyl-2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate, the first fraction, as a white solid (58 mg, 16%). LCMS: (AA) ES−: 474, 476, 1H NMR (400 MHz, CDCl3) δ 7.36 (dd, J=8.3, 4.1 Hz, 1H), 7.17 (d, J=2.1 Hz, 1H), 6.87 (dt, J=9.8, 4.9 Hz, 1H), 6.79 (s, 1H), 5.36-5.23 (m, 1H), 5.03-4.93 (m, 2H), 4.71 (ddt, J=15.2, 5.2, 1.4 Hz, 1H), 4.63 (s, 1H), 4.18 (d, J=1.5 Hz, 1H), 3.74 (s, 3H), 3.46-3.35 (m, 1H).

Workup

  1. additionwas added
  2. customThe mixture was quenched by addition of sat. NH4Cl
  3. extractionextracted with EtOAc
  4. customThe organic layer was separated
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d7f1c80370114301b999a3cba16355ea
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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