Dimethylformamide → Benzyloxyacetyl chloride

HRID 1506700Notes

Reaction equation

HRID 1506700 reaction equation
[CH2:1]([O:8][CH2:9][C:10]([OH:12])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:16])=O.CN(C=O)C>C(Cl)Cl>[CH2:1]([O:8][CH2:9][C:10]([Cl:16])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 290301(Benzyloxy)acetic acid

Product 1

HCID 177085Benzyloxyacetyl chloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyloxyacetic acid (4.6 g, 28.0 mmol, 4.0 mL) in DCM (52 mL) was added oxalyl chloride (7.7 g, 61 mmol, 5.3 mL) and a drop of DMF. The reaction mixture was stirred at room temperature for 4 h. Excess of oxalyl chloride was removed in vacuo to give benzyloxy-acetyl chloride. The crude acyl chloride was diluted into DCM (100 mL) and triethylamine (5.3 mL, 41.6 mmol, 4.2 g) was added followed by 4-fluoroaniline (3.5 g, 32 mmol, 3.0 mL). The reaction mixture was stirred at RT overnight. The reaction was then quenched with 1 M aqueous HCl (100 mL), dried and concentrated in vacuo to give 7.1 g (95%) of 2-benzyloxy-N-(4-fluoro-phenyl)-acetamide (33) as a yellow oil which was used in the next step without purification. The structure was confirmed by 13C NMR (75 MHz, CDCl3) δC 69.2, 73.5, 115.4 (d, JCF=22 Hz), 121.4 (d, JCF=7 Hz), 127.9, 128.2, 128.5, 132.5 (d, JCF=3 Hz), 136.3, 157.6, 160.8, and 167.5.

Workup

  1. customExcess of oxalyl chloride was removed in vacuo

Sources & evidence

ORD record
ord-900dd203691f4761893c0cf3738fc4b5
Source dataset
uspto-grants-2015_12
Patent number
US09220795B2

Reaction notes

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