Formic Acid → Methyl (3-chloro-4-formylphenyl)acetate

HRID 1162512

Reaction equation

HRID 1162512 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]#N)=[C:7]([Cl:13])[CH:6]=1.C(O)=[O:16]>>[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[O:16])=[C:7]([Cl:13])[CH:6]=1

Participants

3

Reactant 2

HCID 284Formic AcidHCID 3564186Methyl 2-(3-chloro-4-cyanophenyl)acetate

Product 1

HCID 59520437Methyl (3-chloro-4-formylphenyl)acetate

Conditions

Temperature
110 °C

Procedure

A solution of (3-chloro-4-cyano-phenyl)acetic acid methyl ester 13 (7.4 g, 35.3 mmol) in 88% formic acid (100 mL) is combined with Raney-alloy (9.0 g) and heated to reflux for 10 hours at 110° C. After cooling to room temperature, the alloy is removed by filtration over Celite. The filtrate is concentrated to ˜10% of the original volume and diluted with EtOAc (250 mL) and washed three times with water (80 mL). The organic layer is dried (MgSO4), filtered and concentrated to afford crude product, which is purified by silica gel chromatography using an EtOAc/hexane gradient to give (3-Chloro-4-formyl-phenyl)-acetic acid methyl ester 14 as a wax-like solid. Another amount of product 14 is collected by reesterification of saponified byproduct (3-Chloro-4-formyl-phenyl)-acetic acid: 1H-NMR (400 MHz, CDCl3) δ=10.31 (s, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.58 (s, 1H), 7.45 (d, J=8.0 Hz, 1H), 3.86 (s, 3H), 3.64 (s, 2H). MS calculated for C10H10ClO3 (M+H+) 213.0, found 213.3.

Workup

  1. temperatureheated
  2. temperatureAfter cooling to room temperature
  3. customthe alloy is removed by filtration over Celite
  4. concentrationThe filtrate is concentrated to ˜10% of the original volume
  5. additiondiluted with EtOAc (250 mL)
  6. washwashed three times with water (80 mL)
  7. dry with materialThe organic layer is dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford crude product, which
  11. customis purified by silica gel chromatography

Sources & evidence

ORD record
ord-d2bbdbb85910429bbc057a4e7fb8425c
Source dataset
uspto-grants-2010_10
Patent number
US07820705B2

Linked notes

Loading…