Pyridine → N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl]amino]thio]-L-proline, methyl ester

HRID 652602Notes

Reaction equation

HRID 652602 reaction equation
[S:1](Cl)Cl.Cl.[NH:5]1[CH2:13][CH2:12][CH2:11][C@H:6]1[C:7]([O:9][CH3:10])=[O:8].N1C=CC=CC=1.[F:20][C:21]1[CH:27]=[C:26]([O:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][C:30]=2[Cl:39])[CH:25]=[CH:24][C:22]=1[NH2:23]>ClCCl.C(OCC)C.C(N(CC)CC)C>[Cl:39][C:30]1[CH:31]=[C:32]([C:35]([F:37])([F:36])[F:38])[CH:33]=[CH:34][C:29]=1[O:28][C:26]1[CH:25]=[CH:24][C:22]([NH:23][S:1][N:5]2[CH2:13][CH2:12][CH2:11][C@H:6]2[C:7]([O:9][CH3:10])=[O:8])=[C:21]([F:20])[CH:27]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 25353Sulfur dichlorideHCID 2733200methyl L-prolinate hydrochlorideHCID 15595105Benzenamine, 4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluoro-

Product 1

HCID 131714973N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl]amino]thio]-L-proline, methyl ester

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent4×HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

A solution of 11.3 g of sulphur dichloride in 20 ml of dichloromethane was added at room temperature over 15 minutes to a stirred solution of 16.6 g of L-proline, methyl ester hydrochloride in 50 ml of the same solvent, following which a solution of 17.4 g of pyridine in 20 ml of the same solvent was added to the reaction mixture over 30 minutes. After stirring overnight, the mixture was diluted with 150 ml of diethyl ether, filtered, and stripped of solvent to leave 17.8 g of the crude product. 4.3 g of this product was dissolved in 10 ml of diethyl ether and added over 15 minutes at room temperature to a stirred mixture of 6.1 g of 31, 2.2 g of triethylamine and 50 ml of diethyl ether. After stirring at room temperature for 30 minutes, 250 ml of diethyl ether was added, and the mixture was washed with water, dried and stripped of solvent. The residue was chromatographed over silica using a mixture of diethyl ether and petroleum ether as eluent, to give 34, as a brown oil.

Workup

  1. additionwas added to the reaction mixture over 30 minutes
  2. filtrationfiltered
  3. customto leave 17.8 g of the crude product
  4. stirringAfter stirring at room temperature for 30 minutes
  5. washthe mixture was washed with water
  6. customdried
  7. customThe residue was chromatographed over silica using
  8. additiona mixture of diethyl ether and petroleum ether as eluent

Sources & evidence

ORD record
ord-7dbd8598a6c74ee0a104af62f2540061
Source dataset
uspto-grants-1987_06
Patent number
US04672139

Reaction notes

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