Water → HCID 86755714, compound

HRID 1873213Notes

Reaction equation

HRID 1873213 reaction equation
[Br:1][C:2]1[C:14]2[S:13][C:12]3[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=3[C:10]=2[C:9]([C:19]2[C:20]([F:27])=[C:21]([OH:26])[C:22]([F:25])=[CH:23][CH:24]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:35][C:36]([O:38][CH3:39])=[O:37].O>CN(C)C=O>[Br:1][C:2]1[C:14]2[S:13][C:12]3[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=3[C:10]=2[C:9]([C:19]2[C:20]([F:27])=[C:21]([C:22]([F:25])=[CH:23][CH:24]=2)[O:26][CH2:35][C:36]([O:38][CH3:39])=[O:37])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]2

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 18687831HCID 18687831, compound

Product 1

HCID 86755714HCID 86755714, compoundYield 85.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension 3-(6-bromo-benzo[b]naphtho[2,3-d]thiophen- 11-yl)-2,6 difluoro-phenol (0.200 g, 0.453 mmol) and potassium carbonate (0.085, 0.612 mmol) in N,N-dimethylformamide (2 mL) was added methyl bromoacetate (0.086 mL, 0.906 mmol) dropwise at room temperature under a dry nitrogen atmosphere. After stirring 2.5 hours the reaction mixture was combined with water (50 mL) and the organics were extracted with ether. The extract was combined with silica gel, the solvent was removed and the adsorbate was flash chromatographed (90/10 petroleum ether/ethyl acetate). The solvents were chased with benzene (2×) and petroleum ether to give [3-(6-bromo-benzo[b]naphtho[2, 3-d]thiophen-11-yl)-2, 6-difluoro-phenoxy]-acetic acid, methyl ester as a white solid (0.198 g, 85%). To a solution of this methyl ester (0.190 g, 0.370 mmol) in tetrahydrofuran (3 mL) and methanol (1 mL) was added a 1 N aqueous solution of potassium hydroxide (0.55 mL, 0.55 mmol) dropwise at room temperature. After stirring 1 hour the solvents were removed and water was added to the solid residue. The aqueous mixture was acidified with 10% HCl and the organics were extracted with ether. After several minutes of vigorous shaking the layers were separated and the organic layer was washed with water and concentrated. The residue was chased with benzene and dried in vacuo to give the title compound as a white solid (0.177g, 95%): mp 195-197° C.: NMR (400 MHz, DMSO-d6): 8 13.11 (broad s, 1 H), 8.31 (d, J=8 Hz, 1 H), 8.09 (d, J=8 Hz, 1 H), 7.83-7.79 (m, 1 H), 7.64-7.46 (m, 4 H), 7.31-7.27 (m, 1 H), 7.23-7.17 (m, 1 H), 6.81 (d, J=8 Hz, 1 H), 4.89 (s, 2 H); MS(-FAB): (M-H): one bromine pattern observed: 497/499 (35%138%); HRMS: Calc. for C24H13BrF2O3S M+: 497.97368, measured mass: 497.97787, mass deviation 4.19 mmu; Anal. HPLC 97% pure; Anal. Calc. for C24H13BrF203S: C, 57.72, H, 2.62% N, 0.00. Found: C, 56.77, H, 2.79% N, 0.00.

Workup

  1. extractionthe organics were extracted with ether
  2. customthe solvent was removed
  3. customchromatographed (90/10 petroleum ether/ethyl acetate)

Sources & evidence

ORD record
ord-0626d873e7514128aa78a32629f5bd89
Source dataset
uspto-grants-2000_08
Patent number
US06110962

Reaction notes

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