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

HRID 2363262Notes

Reaction equation

HRID 2363262 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 (44.1 μL. 0.5 mmol) and t-butyl alcohol (46.5 μL) were combined in ether (1 mL) and 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 (2 mL). (2S,4S)-4-amino-5-(2′-fluorobiphenyl-4-yl)-2-hydroxymethylpentanoic acid ethyl ester (HCl salt; 120 mg, 0.3 mmol) was combined with 1-butanol (3 mL) and 4 M of HCl in 1,4-dioxane (3 mL) and stirred at 60° C. for 2 hours. The solvent were evaporated and azeotroped with toluene (2×). and the product was dissolved in Et3N (155 μL) and DCM, then combined with the chloro-oxo-acetic acid t-butyl ester. The resulting mixture was stirred for 20 minutes at room temperature. The solvent was evaporated and the residue was redissolved in 1:1 TFA:DCM, and stirred for minutes at 40° C. AcOH was added and the product was purified by preparative HPLC to yield the title compound (30 mg, purity 95%). MS m/z [M+H]+ calc'd for C24H28FNO6, 446.19. found 446.4.

Workup

  1. customThe solvent was evaporated under vacuum

Sources & evidence

ORD record
ord-c24f403c20734a03847fca16116d7e54
Source dataset
uspto-grants-2014_04
Patent number
US08691868B2

Reaction notes

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