Hydrogen chloride-ethyl acetate → (R)-N-(3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide hydrochloride

HRID 2202273Notes

Reaction equation

HRID 2202273 reaction equation
[ClH:1].C(OCC)(=O)C.[F:8][C:9]1[CH:10]=[C:11]([NH:22][C:23]([C@H:25]2[C:34]3[C:29](=[CH:30][C:31]([O:35][CH2:36][CH3:37])=[CH:32][CH:33]=3)[CH2:28][CH2:27][N:26]2C(OC(C)(C)C)=O)=[O:24])[CH:12]=[C:13]([F:21])[C:14]=1[C:15]([CH3:20])([CH3:19])[CH2:16][O:17][CH3:18]>C(OCC)(=O)C>[ClH:1].[F:8][C:9]1[CH:10]=[C:11]([NH:22][C:23]([C@H:25]2[C:34]3[C:29](=[CH:30][C:31]([O:35][CH2:36][CH3:37])=[CH:32][CH:33]=3)[CH2:28][CH2:27][NH:26]2)=[O:24])[CH:12]=[C:13]([F:21])[C:14]=1[C:15]([CH3:19])([CH3:20])[CH2:16][O:17][CH3:18]

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 131735745tert-butyl (R)-1-((3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)carbamoyl)-6-ethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 118622727(R)-N-(3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide hydrochlorideYield 102%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4N Hydrogen chloride/ethyl acetate (5 mL) was added to a solution of tert-butyl (R)-1-((3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)carbamoyl)-6-ethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (1.02 g, 1.97 mmol) in ethyl acetate (2 mL), and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the precipitate was collected by filtration with hexane to give (R)—N-(3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide hydrochloride (0.917 g, 2.016 mmol, 102%) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. filtrationthe precipitate was collected by filtration with hexane

Sources & evidence

ORD record
ord-5f5b97e307834305afeeda927bb6395c
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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