Oxalyl chloride → HCID 20773312, compound

HRID 1814801Notes

Reaction equation

HRID 1814801 reaction equation
C(Cl)(=O)C(Cl)=O.[OH:7][C@@:8]([CH3:16])([C:12]([F:15])([F:14])[F:13])[C:9](O)=[O:10].[CH3:17][S:18][C:19]1[CH:24]=[CH:23][C:22]([S:25][C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][CH:34]=2)[NH:31][CH2:30][CH2:29]3)=[CH:21][CH:20]=1>C(Cl)Cl.CN(C=O)C>[CH3:17][S:18][C:19]1[CH:20]=[CH:21][C:22]([S:25][C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][CH:34]=2)[N:31]([C:9](=[O:10])[C@:8]([OH:7])([CH3:16])[C:12]([F:15])([F:14])[F:13])[CH2:30][CH2:29]3)=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 2760712(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acidHCID 22498835HCID 22498835, compound

Product 1

HCID 20773312HCID 20773312, compoundYield 62.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (0.35 ml, 4.0 mmol) was added to a stirred suspension of (R)-(+)-2-hydroxy-2-methyl-3,3,3-trifluoropropanoic acid (0.58 g, 3.7 mmol) (Method A) in DCM (10 ml) containing DMF (1 drop). The mixture was stirred at ambient temperature for 18 hours and was then added to a solution of 5-(4-methylsulphanylphenylsulphanyl)indoline (1.03 g) (Method B) and 2,6-diphenylyridine (0.84 g, 3.64 mmol) in DCM (20 ml). The mixture was stirred for 16 hours, volatile material was removed by evaporation, and the residue was purified by flash column chromatography on silica gel eluting with 10-20% EtOAc/iso-hexane to give the title compound (0.935 g, 2.3 mmol) as a solid. NMR: 1.80 (s, 3H), 2.50 (s, 3H), 3.11-3.19 (m, 2H), 4.19-4.29 (m, 1H), 4.38-4.47 (m, 1H), 4.86 (s, 1H), 7.19-7.27 (m, 6H), 8.20 (d, 1H); m/z (+ve ESP): 414 (M+H)+.

Workup

  1. stirringThe mixture was stirred for 16 hours
  2. customvolatile material was removed by evaporation
  3. customthe residue was purified by flash column chromatography on silica gel eluting with 10-20% EtOAc/iso-hexane

Sources & evidence

ORD record
ord-0534a6f3259e4bd99c3509d9ef7582f7
Source dataset
uspto-grants-2005_04
Patent number
US06878712B1

Reaction notes

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