Oxalyl chloride → (R)-N-(2-chloro4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 2301028Notes

Reaction equation

HRID 2301028 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].[Cl:17][C:18]1[CH:24]=[C:23]([I:25])[CH:22]=[CH:21][C:19]=1[NH2:20].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>C(Cl)Cl.CN(C=O)C>[Cl:17][C:18]1[CH:24]=[C:23]([I:25])[CH:22]=[CH:21][C:19]=1[NH:20][C:9](=[O:10])[C@:8]([OH:7])([CH3:16])[C:12]([F:15])([F:14])[F:13]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 685102,6-Di-tert-butylpyridineHCID 2829302-Chloro-4-iodoanilineHCID 2760712(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid

Product 1

HCID 54268602(R)-N-(2-chloro4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 73.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (1.07 ml) was added dropwise to a stirred suspension of (R)-(+)-2-hydroxy-2-methyl-3,3,3-trifluoropropanoic acid (Method 9) (1.95 g) in DCM (42 ml) and DMF (0.8 ml). The mixture was stirred at ambient temperature for 2 hours and was then added over 35 minutes to a solution of 2-chloro-4-iodoaniline (2.5 g) and 2,6-di-t-butylpyridine (2.94 ml) in DCM (40 ml) and stirred a further 18 hours. Volatile material was removed by evaporation and the residue was purified by flash chromatography on silica gel eluting with DCM to give the title compound (2.85 g) as a solid. NMR: 1.6 (s, 3H), 7.7 (m, 2H), 7.8 (d, 1H), 7.9 (brs, 1H); MS (ESP−): 392.

Workup

  1. stirringstirred a further 18 hours
  2. customVolatile material was removed by evaporation
  3. customthe residue was purified by flash chromatography on silica gel eluting with DCM

Sources & evidence

ORD record
ord-266fb2fdc5be4881b9d96f76fb109ad9
Source dataset
uspto-grants-2002_12
Patent number
US06498275B1

Reaction notes

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