tert-Butanol → tert-Butyl 2-chloro-2-oxoacetate

HRID 1746380Notes

Reaction equation

HRID 1746380 reaction equation
[C:1](Cl)(=[O:5])[C:2]([Cl:4])=[O:3].[C:7]([OH:11])([CH3:10])([CH3:9])[CH3:8]>CCOCC>[C:7]([O:11][C:1](=[O:5])[C:2]([Cl:4])=[O:3])([CH3:10])([CH3:9])[CH3:8]

Participants

4

Reactant 2

HCID 6386tert-ButanolHCID 65578Oxalyl chloride

Product 1

HCID 11126621tert-Butyl 2-chloro-2-oxoacetate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Oxalyl chloride (232 μL, 2.8 mmol) and t-butyl alcohol (228 μL) were combined in ether (6.7 mL) under nitrogen at 0° C. The resulting mixture was stirred for 30 minutes at room temperature. The solvent was evaporated under vacuum to form chloro-oxo-acetic acid t-butyl ester, which was then dissolved in DCM (10 mL) and combined with (2S,4S)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-pentanoic acid ethyl ester (HCl salt; 667 mg, 1.8 mmol), which had been dissolved in DCM with Et3N (2.6 mL) at 0° C. The resulting mixture was stirred for 5 minutes at room temperature. The crude product was concentrated, dissolved in DCM and purified by flash chromatography (20-80% EtOAc/hexanes). The solvent was removed and the residue was dissolved in DCM (5 mL) and TFA (1 mL), and stirred for 1 hour. The product was dried under vacuum and purified by preparative HPLC to yield the title compound (135 mg, purity 95%). MS m/z [M+H]+ calc'd for C22H25NO6, 400.17; found 400.2.

Workup

  1. customThe solvent was evaporated under vacuum

Sources & evidence

ORD record
ord-0731716cef60484ba8410b18cd52e795
Source dataset
uspto-grants-2015_10
Patent number
US09150500B2

Reaction notes

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