Phosphorus oxychloride → HCID 118252523, compound

HRID 1485882Notes

Reaction equation

HRID 1485882 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C@H:9]1[C:17](O)=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:20][C:21]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:22]=1[NH2:23].O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C@H:9]1[C:17](=[O:18])[NH:23][C:22]1[C:21]([F:20])=[CH:27][CH:26]=[CH:25][C:24]=1[F:28])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 796472,6-DifluoroanilineHCID 40418378HCID 40418378, compound

Product 1

HCID 118252523HCID 118252523, compoundYield 69.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To the solution of (S)-2-(tert-butoxycarbonyl)isoindoline-1-carboxylic acid (300 mg, 1.14 mmol, Eq: 1.00) and 2,6-difluoroaniline (177 mg, 1.37 mmol, Eq: 1.2) in pyridine (3.00 mL) at 0° C. was added POCl3 (262 mg, 159 μL, 1.71 mmol, Eq: 1.5). The mixture was warmed to RT and stirred for 2 h. The mixture was evaporated, water was added and the mixture extracted with EtOAc. The combined organics were washed with water, brine, dried with MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography to give (S)-1-(2,6-difluoro-phenylcarbamoyl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (298 mg) as a light yellow foam.

Workup

  1. customThe mixture was evaporated
  2. additionwater was added
  3. extractionthe mixture extracted with EtOAc
  4. washThe combined organics were washed with water, brine
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-a765345e4058466cb949b736e84b55a5
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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