Boron Trichloride → Methyl 4-(3,5-dichloro-4-hydroxybenzamido)benzoate

HRID 62716Notes

Reaction equation

HRID 62716 reaction equation
C([O:8][C:9]1[C:27]([Cl:28])=[CH:26][C:12]([C:13]([NH:15][C:16]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=2)=[O:14])=[CH:11][C:10]=1[Cl:29])C1C=CC=CC=1.B(Cl)(Cl)Cl>C(Cl)Cl>[Cl:28][C:27]1[CH:26]=[C:12]([CH:11]=[C:10]([Cl:29])[C:9]=1[OH:8])[C:13]([NH:15][C:16]1[CH:17]=[CH:18][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:24][CH:25]=1)=[O:14]

Participants

4

Reactant 2

HCID 25135Boron TrichlorideHCID 67041711HCID 67041711, compound

Product 1

HCID 4825911Methyl 4-(3,5-dichloro-4-hydroxybenzamido)benzoateYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 4-(4-(benzyloxy)-3,5-dichlorobenzamido)benzoate (4) (8.8 g, 20.5 mmol) in DCM (500 mL) was cooled to 0° C. and treated dropwise with boron trichloride (20.5 mL, 20.5 mmol, 1 M in DCM). The mixture was then allowed to stir at RT for 12 h. The mixture was cooled in an ice bath then quenched by addition of water (150 mL). The resultant mixture was partitioned between EtOAc (200 mL) and H2O (100 mL). The aqueous phase was extracted with EtOAc (2×75 mL) and the combined organic phases washed successively with water (50 mL) and brine (50 mL), then dried over MgSO4 and filtered. The solvent was removed in vacuo. The residue was crystallised from isohexane/EtOAc to afford methyl 4-(3,5-dichloro-4-hydroxybenzamido)benzoate (5) (5.81 g, 84%): m/z 338 (M−H)− (ES−). 1H NMR (400 MHz, DMSO-d6) δ: 11.06 (1H, s), 10.52 (1H, s), 8.06 (2H, s), 8.00 (2H, d), 7.95 (2H, d), 3.88 (3H, s).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. customthen quenched by addition of water (150 mL)
  3. customThe resultant mixture was partitioned between EtOAc (200 mL) and H2O (100 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (2×75 mL)
  5. washthe combined organic phases washed successively with water (50 mL) and brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customThe solvent was removed in vacuo
  9. customThe residue was crystallised from isohexane/EtOAc

Sources & evidence

ORD record
ord-d5eba37f583c45bb9c81c0a1edcdbbdc
Source dataset
uspto-grants-2016_09
Patent number
US09447028B2

Reaction notes

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