2-Chloroethyl chloroformate → 3-(6-Acetyl-4-chloro-3'-fluoro-3-methylbiphenyl-2-yl)-1,3-oxazolidin-2-one

HRID 510840Notes

Reaction equation

HRID 510840 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[C:6]([C:15](=[O:17])[CH3:16])[CH:5]=[C:4]([Cl:18])[C:3]=1[CH3:19].[CH2:20]([O:23][C:24](Cl)=[O:25])[CH2:21]Cl.CC(C)([O-])C.[K+]>CN(C)C1C=CN=CC=1.O1CCCC1>[C:15]([C:6]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[C:2]([N:1]2[CH2:21][CH2:20][O:23][C:24]2=[O:25])[C:3]([CH3:19])=[C:4]([Cl:18])[CH:5]=1)(=[O:17])[CH3:16]

Participants

6

Reactant 3

HCID 123052-Chloroethyl chloroformateHCID 23665647Potassium tert-butoxideHCID 583684301-(6-Amino-4-chloro-3'-fluoro-5-methylbiphenyl-2-yl)ethanone

Product 1

HCID 866667723-(6-Acetyl-4-chloro-3'-fluoro-3-methylbiphenyl-2-yl)-1,3-oxazolidin-2-oneYield 10.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 1-(6-amino-4-chloro-3′-fluoro-5-methylbiphenyl-2-yl)ethanone (100 mg, 0.4 mmol) and 4-dimethylaminopyridine (53 mg, 0.43 mmol) in tetrahydrofuran (1 mL) was added 2-chloroethyl chloridocarbonate (0.041 mL, 0.40 mmol). The mixture was stirred at room temperature overnight. To the mixture was added 1.0 M potassium tert-butoxide in tetrahydrofuran (0.79 mL) at 0° C., and the resulting mixture stirred at room temperature for 2 hours, then quenched with aq. ammonium chloride, extracted with ethyl acetate. The combined organic layers were washed with brine, dried, and evaporated. The filtrate was applied on silica gel, eluting with 0 to 60% ethyl acetate in hexane, to give the desired product (14 mg, 10%). LCMS calculated for C18H16ClFNO3 (M+H)+: m/z=348.1. found: 348.0.

Workup

  1. stirringthe resulting mixture stirred at room temperature for 2 hours
  2. customquenched with aq. ammonium chloride
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. customdried
  6. customevaporated
  7. washeluting with 0 to 60% ethyl acetate in hexane

Sources & evidence

ORD record
ord-91bd185a75854b099fb88102c3c795a6
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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