Oxalyl chloride → (R)-N-(4-[Anilinosulphonyl]-2,5-dimethoxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide

HRID 1267725

Reaction equation

HRID 1267725 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].[NH:35]([S:42]([C:45]1[C:51]([O:52][CH3:53])=[CH:50][C:48]([NH2:49])=[C:47]([O:54][CH3:55])[CH:46]=1)(=[O:44])=[O:43])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>C(Cl)Cl.CN(C=O)C>[NH:35]([S:42]([C:45]1[C:51]([O:52][CH3:53])=[CH:50][C:48]([NH:49][C:26](=[O:34])[C@:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[C:47]([O:54][CH3:55])[CH:46]=1)(=[O:44])=[O:43])[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 685102,6-Di-tert-butylpyridineHCID 1041434-Amino-2,5-dimethoxy-N-phenylbenzenesulfonamideHCID 69539468(R)-N-[2,3-Dichloro-4-(4-hydroxypiperidin-1-ylsulphonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide

Product 1

HCID 69539452(R)-N-(4-[Anilinosulphonyl]-2,5-dimethoxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamideYield 43.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (0.13 ml, 1.5 mmol) was added to a stirred suspension of (R)-(+)-2-hydroxy-2-methyl-3,3,3-trifluoropropanoic acid (0.154 g, 0.97 mmol) (Method 3) in DCM (10 ml) containing DMF (1 drop). The mixture was stirred at ambient temperature overnight, then 4-[anilinosulphonyl]-2,5-dimethoxyaniline (200 mg, 0.65 mmol)† and 2,6-di-t-butylpyridine (0.14 ml, 0.66 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 solid (0.125 g, 0.28 mmol); M.p: 194-195° C., NMR: 1.7 (s, 3H), 3.8 (s, 3H), 4.1 (s, 3H), 6.9 (s, 1H), 7.05 (m, 3H), 7.2 (m, 3H), 8.3 (s, 1H), 9.1 (brs, 1H); m/z 447.

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-4831c1e255ef4e51bd0d61664b1763a7
Source dataset
uspto-grants-2003_04
Patent number
US06552225B1

Linked notes

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