Tetrahydrofuran → 1-{2-[3-(3,4,5-Trichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]-4-(trifluoromethyl)-1,3-thiazol-5-yl}methanamine

HRID 1776991Notes

Reaction equation

HRID 1776991 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:26]([F:29])([F:28])[F:27])[CH2:14][CH2:13][N:12]([C:15]3[S:16][C:17]([CH2:24]O)=[C:18]([C:20]([F:23])([F:22])[F:21])[N:19]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].O1CCCC1.CS(Cl)(=O)=O.O.[NH3:41]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:26]([F:29])([F:28])[F:27])[CH2:14][CH2:13][N:12]([C:15]3[S:16][C:17]([CH2:24][NH2:41])=[C:18]([C:20]([F:23])([F:22])[F:21])[N:19]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 31297Methanesulfonyl chlorideHCID 12896473Azane;hydrateHCID 59453386{2-[3-(3,4,5-Trichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]-4-(trifluoromethyl)-1,3-thiazol-5-yl}methanol

Product 1

HCID 594533691-{2-[3-(3,4,5-Trichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]-4-(trifluoromethyl)-1,3-thiazol-5-yl}methanamineYield 45%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

{2-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-4-(trifluoro-methyl)-1,3-thiazol-5-yl}methanol (1.05 g) was added to tetrahydrofuran (30 mL). Then, tetrahydrofuran solution (10 mL) comprising methanesulfonyl chloride (0.3 g) was added dropwise thereto under ice cooling. After the dropwise addition was completed, the reaction solution was stirred at room temperature for one hour. The resulting solution was added dropwise to a mixture solution, which was separately prepared to contain 28% ammonia water (50 mL), tetrahydrofuran (100 mL), and methanol (100 mL), under ice cooling. After stirring the mixture at room temperature for 12 hours, the reaction solution was poured over ice water, and then extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The solvent was evaporated off under reduced pressure, and the residue was then purified by a silica gel chromatography to obtain the title compound (0.4 g, 45%).

Workup

  1. additionwas added dropwise
  2. additionAfter the dropwise addition
  3. additionThe resulting solution was added dropwise to a mixture solution, which
  4. customwas separately prepared
  5. stirringAfter stirring the mixture at room temperature for 12 hours
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. customThe solvent was evaporated off under reduced pressure
  9. customthe residue was then purified by a silica gel chromatography

Sources & evidence

ORD record
ord-e1efaa6a3bb84442885cc0379957b442
Source dataset
uspto-grants-2016_02
Patent number
US09266830B2

Reaction notes

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