N-bromobutanimide → HCID 86730632, compound

HRID 332851Notes

Reaction equation

HRID 332851 reaction equation
[F:1][C:2]1[C:7]2[S:8][C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[CH:10][C:6]=2[CH:5]=[CH:4][C:3]=1[O:19][CH3:20].[F:21][C:22]1[C:38]([O:39][CH3:40])=[C:37]([F:41])[C:25]2[S:26][C:27]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)=[CH:28][C:24]=2[CH:23]=1.C1C(=O)N([Br:49])C(=O)C1>C1COCC1.C(Cl)Cl.[O-]S([O-])(=S)=O.[Na+].[Na+]>[Br:49][C:10]1[C:6]2[CH:5]=[CH:4][C:3]([O:19][CH3:20])=[C:2]([F:1])[C:7]=2[S:8][C:9]=1[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1.[Br:49][C:28]1[C:24]2[CH:23]=[C:22]([F:21])[C:38]([O:39][CH3:40])=[C:37]([F:41])[C:25]=2[S:26][C:27]=1[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1

Participants

8

Reactant 3

HCID 67184N-bromobutanimideHCID 86730634HCID 86730634, compoundHCID 86730635HCID 86730635, compound

Product 2

HCID 86730632HCID 86730632, compoundYield 43.6%HCID 867306333-Bromo-5,7-difluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiopheneYield 24.62%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 24477Sodium ThiosulfateSolvent

Conditions

Temperature
0 °C

Procedure

To a round bottom flask, an unseparated mixture of 7-fluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene and 5,7-difluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene (380 mg, 1.318 mmol) was dissolved in THF (10 mL) and the solution was cooled to 0° C. To the solution was added NBS (237 mg, 1.331 mmol). The reaction mixture was stirred at 0° C. for 1 h then warmed to room temperature and stirred for an additional 2 h. The reaction mixture was concentrated to afford the crude product. The crude product was diluted with DCM and sat. Na2S2O3 (sodium thiosulfate). The organic layer was collected (phase separator) and concentrated. The reaction mixture was diluted with water and DCM. The organic phase was collected (phase separator) and concentrated to afford the crude product. The crude material was purified by column chromatography (SiO2, 0-5% Heptanes/EtOAc) to afford 3-bromo-7-fluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene (211 mg, 0.575 mmol, 43.6% yield) and 3-bromo-5,7-difluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene (125 mg, 0.324 mmol, 24.62% yield). 3-bromo-7-fluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene: 1H NMR (400 MHz, CDCl3) δ ppm=7.56-7.66 (m, 2H), 7.46 (dd, J=1.01, 8.59 Hz, 1H), 7.11 (dd, J=7.58, 8.59 Hz, 1H), 6.90-6.97 (m, 2H), 3.92 (s, 3H), 3.79 (s, 3H). 3-bromo-5,7-difluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene: 1H NMR (400 MHz, CDCl3) δ ppm=7.53-7.68 (m, 2H), 7.48 (d, J=8.59 Hz, 1H), 7.15-7.27 (m, 1H), 7.07 (dt, J=2.53, 8.59 Hz, 1H), 3.98 (s, 3H), 4.02 (s, 3H).

Workup

  1. temperaturethen warmed to room temperature
  2. stirringstirred for an additional 2 h
  3. concentrationThe reaction mixture was concentrated
  4. customto afford the crude product
  5. customThe organic layer was collected (phase separator)
  6. concentrationconcentrated
  7. additionThe reaction mixture was diluted with water and DCM
  8. customThe organic phase was collected (phase separator)
  9. concentrationconcentrated
  10. customto afford the crude product
  11. customThe crude material was purified by column chromatography (SiO2, 0-5% Heptanes/EtOAc)

Sources & evidence

ORD record
ord-75a158d1e0564ccca05873a38e6d697b
Source dataset
uspto-grants-2014_11
Patent number
US08877801B2

Reaction notes

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