Hydrochloric Acid → HCID 69135125, compound

HRID 1828694Notes

Reaction equation

HRID 1828694 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:8]=[C:7]([S:9][C:10](=S)OCC)[CH:6]=[CH:5][C:4]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[OH-].[Na+].Cl.[BH4-].[Na+].[CH3:28][O:29][C:30](=[O:39])[C:31]1[CH:36]=[CH:35][C:34](CBr)=[CH:33][CH:32]=1>CCO.CCOC(C)=O.CN(C=O)C>[CH3:28][O:29][C:30](=[O:39])[C:31]1[CH:36]=[CH:35][C:34]([CH2:10][S:9][C:7]2[CH:6]=[CH:5][C:4]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:8]=2)=[CH:33][CH:32]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 256687Methyl 4-(bromomethyl)benzoateHCID 4311764Sodium borohydrideHCID 86595994HCID 86595994, compound

Product 1

HCID 69135125HCID 69135125, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of dithiocarbonic acid O-ethyl ester S-(2-trifluoromethyl-biphenyl-4-yl) ester (128 mg, 0.3738 mmol) in EtOH (5 mL) is added aqueous NaOH (1 N, 5 mL). The mixture is heated at 65° C. for 3 h. After cooling to room temperature, 1 N HCl (aq) is added until the reaction pH is adjusted to ca. pH=5. The reaction is diluted with EtOAc and washed with H2O followed by saturated aqueous NaCl. The organic solution is dried over Na2SO4. After concentration, the crude 2-trifluoromethyl-biphenyl-4-thiol product obtained (64 mg, 0.2519 mmol) is dissolved in EtOH (5 mL). NaBH4 (19 mg, 0.5039 mmol, 2 eq.) is added to this solution. The resulting mixture is stirred at room temperature for 25 min at which point methyl-4-(bromomethyl)benzoate (58 mg, 0.2519 mmol, 1 eq.) in DMF (1.5 mL) is added to the reaction. The mixture is stirred at room temperature an additional 30 min. The EtOH is removed under vacuum. The resulting DMF solution is diluted with EtOAc and washed with H2O followed by saturated aqueous NaCl. The organic solution is dried over Na2SO4. After concentration, the residue is purified by silica gel chromatography (3:1 hexanes/EtOAc) to give 4-(2-trifluoromethyl-biphenyl-4-ylsulfanylmethyl)-benzoic acid methyl ester. [MS: (ES+) 425.1 (M+23)+].

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with H2O
  3. dry with materialThe organic solution is dried over Na2SO4
  4. concentrationAfter concentration
  5. customthe crude 2-trifluoromethyl-biphenyl-4-thiol product obtained (64 mg, 0.2519 mmol)
  6. additionis added to the reaction
  7. customThe EtOH is removed under vacuum
  8. additionThe resulting DMF solution is diluted with EtOAc
  9. washwashed with H2O
  10. dry with materialThe organic solution is dried over Na2SO4
  11. concentrationAfter concentration
  12. customthe residue is purified by silica gel chromatography (3:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-d1c15e08fec5486eb66ec2d92ff83496
Source dataset
uspto-grants-2006_06
Patent number
US07060697B2

Reaction notes

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