Acetyl chloride → HCID 15125730, compound

HRID 129592Notes

Reaction equation

HRID 129592 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]([S:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:21][C:22]([OH:24])=[O:23])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25](Cl)(=O)C>CO>[O:1]([C:8]1[CH:9]=[C:10]([S:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:21][C:22]([O:24][CH3:25])=[O:23])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 15125729HCID 15125729, compound

Product 1

HCID 15125730HCID 15125730, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

2-Mercaptophenylacetic acid was prepared by a method described in the chemical literature (see D. Papa et al, J. Org. Chem., 1949, 24, 723, R. H. Glauert and F. G. Mann, J. Chem. Soc., 1952, 2127 and references therein). 2-Mercaptophenylacetic acid (1.68 g) was added to a stirred solution of sodium hydroxide (0.8 g) in methanol (10 ml), (compare D. C. Atkinson et al, J. Med. Chem., 1983, 26, 1361). The resulting orange solution was stirred at room temperature for 90 minutes then concentrated under reduced pressure, removing the final residues of methanol by azeotroping with toluene, to leave a yellow solid. Cuprous chloride (0.2 g) and a solution of 3-phenoxybromobenzene (2.49 g, prepared from 3-phenoxyphenol and triphenylphosphine dibromide by the method described by J. P. Schaefer et al, Org. Synth., Coll. Vol.5, 142) in DMF (10 ml) were added successively to a stirred solution of this yellow solid in DMF (20 ml). The resulting mixture was heated at 95° C. for 11/2 hours, at 125° C. for 2 hours, and then at reflux for a further 2 hours. After cooling, the reaction mixture was poured into aqueous sodium hydroxide then washed with ether (×3). The aqueous solution was acidified with concentrated hydrochloric acid and extracted with ether (×3). These extracts were washed with water, dried and concentrated to give a purple oil (2.2 g) consisting mainly of 2-(3-phenoxyphenylthio)phenylacetic acid. A solution of this oil in methanol (20 ml) was added to acidic methanol [prepared by carefully treating methanol (30 ml) with acetyl chloride (3.5 ml)] and the resulting mixture was stirred for 90 minutes at room temperature. The reaction mixture was concentrated and the residue was partitioned between ether and aqueous sodium bicarbonate. The organic layer was separated and washed successively with aqueous sodium hydroxide (×2) and water (×3) then dried and concentrated to give crude methyl 2-(3-phenoxyphenylthio)phenylacetate (2.06 g) as a purple oil.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between ether and aqueous sodium bicarbonate
  3. customThe organic layer was separated
  4. washwashed successively with aqueous sodium hydroxide (×2) and water (×3)
  5. customthen dried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-b674d3d14fe441db9f5c3dba8a359f37
Source dataset
uspto-grants-1995_11
Patent number
US05468857

Reaction notes

Loading…