Phosphorus oxychloride → (S)-2-(1-(5-(4-chlorophenyl)oxazol-2-yl)ethyl)isoindoline-1,3-dione

HRID 57386Notes

Reaction equation

HRID 57386 reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:31])[CH2:14][NH:15][C:16](=O)[C@@H:17]([N:19]2[C:27](=[O:28])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]2=[O:29])[CH3:18])=[CH:9][CH:8]=1>C1(C)C=CC=CC=1.ClCCl>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[O:31][C:16]([C@@H:17]([N:19]3[C:27](=[O:28])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20]3=[O:29])[CH3:18])=[N:15][CH:14]=2)=[CH:9][CH:8]=1

Participants

5

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 90414725(S)-N-(2-(4-chlorophenyl)-2-oxoethyl)-2-(1,3-dioxoisoindolin-2-yl)propanamide

Product 1

HCID 90414733(S)-2-(1-(5-(4-chlorophenyl)oxazol-2-yl)ethyl)isoindoline-1,3-dioneYield 20.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

Phosphoryl trichloride (1.m7 ml, 10.8 mmol) was added to a solution of (S)—N-(2-(4-chlorophenyl)-2-oxoethyl)-2-(1,3-dioxoisoindolin-2-yl)propanamide (2.162 g, 5.83 mmol) in toluene and heated at 110° C. for 15 hours. Dilute with dichloromethane (50 ml), wash with saturated sodium bicarbonate solution, water, brine, dried and concentrated in vacuo. Flash column chromatography (silica, 80 g) eluting with 0-50% EtOAc/DCM afforded the pure product 430 mg (yellow foam). HRMS(B) tR=1.42 min; MS m/z 353.1

Workup

  1. washwash with saturated sodium bicarbonate solution, water, brine
  2. customdried
  3. concentrationconcentrated in vacuo
  4. washFlash column chromatography (silica, 80 g) eluting with 0-50% EtOAc/DCM

Sources & evidence

ORD record
ord-8569a830404d49b583a4c303044a89d5
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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