Trifluoroacetic acid → (R)-N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide

HRID 2202213Notes

Reaction equation

HRID 2202213 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:10]=[C:11]([NH:20][C:21]([C@H:23]2[C:32]3[C:27](=[CH:28][C:29]([O:33][CH3:34])=[CH:30][CH:31]=3)[CH2:26][CH2:25][N:24]2C(OC(C)(C)C)=O)=[O:22])[CH:12]=[C:13]([F:19])[C:14]=1[Si:15]([CH3:18])([CH3:17])[CH3:16].C(=O)([O-])O.[Na+].C(=O)([O-])[O-].[K+].[K+]>>[F:8][C:9]1[CH:10]=[C:11]([NH:20][C:21]([C@H:23]2[C:32]3[C:27](=[CH:28][C:29]([O:33][CH3:34])=[CH:30][CH:31]=3)[CH2:26][CH2:25][NH:24]2)=[O:22])[CH:12]=[C:13]([F:19])[C:14]=1[Si:15]([CH3:17])([CH3:16])[CH3:18]

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 131735727tert-butyl (R)-1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 131735726(R)-N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamideYield 70.8%

Procedure

Cooled TFA (4.5 mL) was added to tert-butyl (R)-1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (439 mg, 0.89 mmol) at room temperature, and the mixture was stirred at room temperature for 2 min. The reaction mixture was poured into ice and aqueous sodium hydrogencarbonate solution, the pH of mixture was adjusted to 8 with potassium carbonate, and the mixture was extracted with ethyl acetate (×3). The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The precipitate was washed with IPE/hexane to give (R)—N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide (246 mg, 0.630 mmol, 70.4%) as white crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (×3)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. washThe precipitate was washed with IPE/hexane

Sources & evidence

ORD record
ord-d1bf1ae007324fa28034e1e096dc722a
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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