2,6-Di-tert-butylpyridine → (R)-N-(2-chloro-3-nitro-4-iodophenyl)-2-trimethylsilyloxy-2-methyl-3,3,3-trifluoropropanamide

HRID 2120371Notes

Reaction equation

HRID 2120371 reaction equation
[I:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([Cl:9])[C:3]=1[N+:10]([O-:12])=[O:11].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C.[F:27][C:28]([F:40])([F:39])[C@@:29]([O:34][Si:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[C:30](Cl)=[O:31]>C(Cl)Cl>[Cl:9][C:4]1[C:3]([N+:10]([O-:12])=[O:11])=[C:2]([I:1])[CH:8]=[CH:7][C:5]=1[NH:6][C:30](=[O:31])[C@:29]([O:34][Si:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[C:28]([F:39])([F:27])[F:40]

Participants

5

Reactant 3

HCID 685102,6-Di-tert-butylpyridineHCID 10586677(S)-3,3,3-trifluoro-2-trimethylsilyloxy-2-methylpropanoyl chlorideHCID 234394594-Iodo-3-nitro-2-chloroaniline

Product 1

HCID 69824807(R)-N-(2-chloro-3-nitro-4-iodophenyl)-2-trimethylsilyloxy-2-methyl-3,3,3-trifluoropropanamideYield 53.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Iodo-3-nitro-2-chloroaniline (Method 70) (1269 mg) and 2,6-di-t-butylpyridine (1.5 ml) were added to a solution of (S)-3,3,3-trifluoro-2-(trimethylsilyloxy)-2-methylpropanoyl chloride (prepared from (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (Method 25) as described in J. Med. Chem., 1999, 42, 2741-2746) (6 mmol) in DCM (40 ml). The mixture was stirred for 3 days at ambient temperature. The volatile material was removed by evaporation and the residue was purified by chromatography eluting with 10% EtOAc in hexane to give the title compound (1160 mg). NMR: 0.27 (s, 9H), 1.70 (s, 3H), 7.70 (d, 1H), 8.05 (d, 1H), 9.72 (brs, 1H); m/z 509.

Workup

  1. customThe volatile material was removed by evaporation
  2. customthe residue was purified by chromatography
  3. washeluting with 10% EtOAc in hexane

Sources & evidence

ORD record
ord-5bb3fd069e264d688d8f22e480cf56f0
Source dataset
uspto-grants-2004_02
Patent number
US06689909B1

Reaction notes

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