Oxalyl chloride → (R)-N-(2,5-Dimethoxy-4-[dimethylaminosulphonyl]phenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide

HRID 1267726Notes

Reaction equation

HRID 1267726 reaction equation
C(Cl)(=O)C(Cl)=O.ClC1C(Cl)=C(S(N2CCC(O)CC2)(=O)=O)C=CC=1N[C:26](=[O:34])[C@:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29].[CH3:35][O:36][C:37]1[CH:43]=[C:42]([S:44]([N:47]([CH3:49])[CH3:48])(=[O:46])=[O:45])[C:41]([O:50][CH3:51])=[CH:40][C:38]=1[NH2:39].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>C(Cl)Cl.CN(C=O)C>[CH3:35][O:36][C:37]1[CH:43]=[C:42]([S:44]([N:47]([CH3:49])[CH3:48])(=[O:46])=[O:45])[C:41]([O:50][CH3:51])=[CH:40][C:38]=1[NH:39][C:26](=[O:34])[C@:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 685102,6-Di-tert-butylpyridineHCID 131531254-Amino-2,5-dimethoxy-N,N-dimethylbenzene-1-sulfonamideHCID 69539468(R)-N-[2,3-Dichloro-4-(4-hydroxypiperidin-1-ylsulphonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide

Product 1

HCID 69539551(R)-N-(2,5-Dimethoxy-4-[dimethylaminosulphonyl]phenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamideYield 68.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (0.15 ml, 1.8 mmol) was added to a stirred suspension of (R)-(+)-2-hydroxy-2-methyl-3,3,3-trifluoropropanoic acid (0.18 g, 1.15 mmol) (Method 3) in DCM (10 ml) containing DMF (1 drop). The mixture was stirred at ambient temperature overnight, then 2,5-dimethoxy-4-[dimethylaminosulphonyl]aniline (200 mg, 0.77 mmol)‡ and 2,6-di-t-butylpyridine (0.19 ml, 0.9 mmol) was added and the resulting mixture stirred a further 2 hours at room temperature. Dichloromethane (25 ml) was added and the mixture was washed with water (2×50 ml) and brine then dried. Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column eluting with 50% EtOAc/iso-hexane to give the title compound as a foam (212 mg, 0.53 mmol); NMR: 1.74 (s, 3H), 2.83 (s, 6H), 3.91 (s, 6H), 7.40 (s, 1H), 8.27 (s, 1H), 9.17 (s, 1H); m/z 399.

Workup

  1. stirringthe resulting mixture stirred a further 2 hours at room temperature
  2. washthe mixture was washed with water (2×50 ml) and brine
  3. customthen dried
  4. customVolatile material was removed by evaporation
  5. customthe residue was purified by chromatography on a silica gel Mega Bond Elut column
  6. washeluting with 50% EtOAc/iso-hexane

Sources & evidence

ORD record
ord-8fc800dcd13a43a28e183e9e3ee8707d
Source dataset
uspto-grants-2003_04
Patent number
US06552225B1

Reaction notes

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