Dichloromethane → HCID 9831417, compound

HRID 1940046Notes

Reaction equation

HRID 1940046 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)=[O:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:23](Cl)(=O)[C:24](Cl)=O.Cl.N[C@H](C([N:37]([CH:45]([CH:52]([CH3:54])[CH3:53])[C:46](=[O:51])[C:47]([F:50])([F:49])[F:48])[C:38](=[O:44])[C@@H:39]1[CH2:43][CH2:42][CH2:41][NH:40]1)=O)C(C)C.C[N:56]1[CH2:61][CH2:60][O:59]CC1.[CH2:62](Cl)Cl>O.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]([C:14]2[CH:15]=[CH:16][C:17]([C:18]([NH:56][C@H:61]([C:60]([N:40]3[CH2:41][CH2:42][CH2:43][C@H:39]3[C:38]([NH:37][CH:45]([CH:52]([CH3:53])[CH3:54])[C:46](=[O:51])[C:47]([F:48])([F:49])[F:50])=[O:44])=[O:59])[CH:23]([CH3:24])[CH3:62])=[O:19])=[CH:21][CH:22]=2)=[O:13])(=[O:9])=[O:10])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6344Dichloromethane2×HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 15200177HCID 15200177, compoundHCID 131720359HCID 131720359, compound

Product 1

HCID 9831417HCID 9831417, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred light suspension of 4-[(4-chlorophenyl)sulfonylaminocarbonyl]benzoic acid (0.68 g, 2.02 mmol; EP Pat. Appl. Publ. No. 0189305 B1) in CH2Cl2 (18 mL) and DMF (2 mL) under argon is added oxalyl chloride (0.18 mL, 2.02 mmol) dropwise. After 50 minutes, add a solution of 51 (0.81 g, 2.02 mmol) and NMM (1.00 mL, 9.07 mmol) in CH2Cl2 (8 mL). Stir for 3 hours and then pour the reaction mixture into H2O (75 mL) and separate the layers. The aqueous phase is extracted with additional EtOAc (2×35 mL) and the combined organic extracts are washed with 1N aqueous hydrochloric acid (2×30 mL) followed by brine (30 mL). Drying (MgSO4) and concentration gives crude 54. Purification by flash chromatography [gradient (54-74%) of EtOAc in hexane containing 1% acetic acid] gives 54 [0.96 g (70%), (1:1::LLL:LLD)] as a white solid foam.

Workup

  1. customseparate the layers
  2. extractionThe aqueous phase is extracted with additional EtOAc (2×35 mL)
  3. washthe combined organic extracts are washed with 1N aqueous hydrochloric acid (2×30 mL)
  4. customDrying
  5. concentration(MgSO4) and concentration
  6. customgives crude 54
  7. customPurification by flash chromatography [gradient (54-74%) of EtOAc in hexane containing 1% acetic acid]

Sources & evidence

ORD record
ord-2e619356766647c79e305129aeab0c57
Source dataset
uspto-grants-1997_12
Patent number
US05698523

Reaction notes

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