Phosphorus oxychloride → HCID 90041107, compound

HRID 1485888Notes

Reaction equation

HRID 1485888 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C@H:9]1[C:18]([OH:20])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:23]=1[NH2:24].O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C@H:9]1[C:18](=[O:20])[NH:24][C:23]1[C:22]([F:21])=[CH:28][CH:27]=[CH:26][C:25]=1[F:29])=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 796472,6-DifluoroanilineHCID 25417906HCID 25417906, compound

Product 1

HCID 90041107HCID 90041107, compoundYield 54.4%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To the solution of (S)-3,4-dihydro-1H-isoquinoline-1,2-dicarboxylic acid 2-tert-butyl ester (500 mg, 1.8 mmol, Eq: 1.00) and 2,6-difluoroaniline (279 mg, 2.16 mmol, Eq: 1.2) in pyridine (10.0 mL) at 0° C. was added POCl3 (415 mg, 252 μL, 2.7 mmol, Eq: 1.5). The mixture was warmed to RT and stirred for 2 h. The solvent 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)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (380 mg) as a white foam.

Workup

  1. customThe solvent 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-a4817c54927345118581b59e3bf09470
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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