Water → 2,6-Difluoro-3-[5-(3-methoxy-phenyl)-benzothiazol-2-ylmethoxy]-benzamide

HRID 415596Notes

Reaction equation

HRID 415596 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][O:11][C:12]3[C:13]([F:22])=[C:14]([C:18]([F:21])=[CH:19][CH:20]=3)[C:15]([NH2:17])=[O:16])=[N:7][C:6]=2[CH:23]=1.O.[CH3:25][O:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:22][C:13]1[C:12]([O:11][CH2:10][C:8]2[S:9][C:5]3[CH:4]=[CH:3][C:2]([C:31]4[CH:30]=[CH:29][CH:28]=[C:27]([O:26][CH3:25])[CH:32]=4)=[CH:23][C:6]=3[N:7]=2)=[CH:20][CH:19]=[C:18]([F:21])[C:14]=1[C:15]([NH2:17])=[O:16]

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2734370(3-Methoxyphenyl)boronic acidHCID 462370143-(5-Bromo-benzothiazol-2-ylmethoxy)-2,6-difluoro-benzamide

Product 1

HCID 594028792,6-Difluoro-3-[5-(3-methoxy-phenyl)-benzothiazol-2-ylmethoxy]-benzamideYield 43.5%

Reagents, catalysts & solvents 2

HCID 21584511triphenylphosphine palladium (II)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To the solution of compound 3-(5-bromo-benzothiazol-2-ylmethoxy)-2,6-difluoro-benzamide (0.300 g, 0.755 mmol) in dry DMF:H2O (5 mL: 2.5 mL), added 3-methoxyphenyl boronic acid (0.228 g, 1.5 mmol), and K3PO4 (0.190 g, 0.9 mmol) under the inert condition at room temperature and degassed for half an hour. Then to the reaction mixture added dichlorobis [(triphenylphosphine)-palladium (II) (0.078 g, 0.075 mmol) and again degassed for half an hour. The reaction mixture was heated at 120° C. for 2 hrs under nitrogen atmosphere. DMF was distilled off, after cooling to r.t. water was added into reaction mixture and extracted with ethyl acetate, The combined organic layers were dried over anhydrous Na2SO4, and evaporated to dryness under reduced pressure. The compound was purified by chromatography on silica (230-400μ) using ethyl acetate/hexane (50:50 as the eluent to provide the title compound as white solid (0.140 g, 43%). 1H NMR (DMSO-d6, 400 MHz); δ 3.85 (s, 3H), 5.72 (s, 2H), 6.97 (t, 1H, J=6.8 Hz (o-coupling), 7.11 (t, 1 H, J=8.8 Hz, (o-coupling), 7.30 (broad s, 1 H), 7.34 (d, 1H, J=8.8 Hz (o-coupling), 7.40 (dd, 2H, J=8.0 Hz (o-coupling), 7.79 (d, 1H, J=8.0 Hz (o-coupling), 7.90 (broad s, 1H), 8.18 (broad s, 1H), 8.21 (d, 1H, J=8.0 Hz); MS ES+ (427.14), HPLC (method 5) Rt=16.48 min.

Workup

  1. customdegassed for half an hour
  2. customagain degassed for half an hour
  3. distillationDMF was distilled off
  4. temperatureafter cooling to r.t. water
  5. additionwas added into reaction mixture
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  8. customevaporated to dryness under reduced pressure
  9. customThe compound was purified by chromatography on silica (230-400μ)

Sources & evidence

ORD record
ord-35136afce9eb4e54bfdaa1c1265cec4c
Source dataset
uspto-grants-2012_01
Patent number
US08088791B2

Reaction notes

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