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

HRID 2202278Notes

Reaction equation

HRID 2202278 reaction equation
[ClH:1].C(OCC)(=O)C.[CH2:8]([O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C@H:17]([C:21](=[O:38])[NH:22][C:23]1[CH:28]=[C:27]([F:29])[C:26]([C:30]([CH3:36])([CH3:35])[CH2:31][O:32][CH2:33][CH3:34])=[C:25]([F:37])[CH:24]=1)[N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]2)[CH3:9]>C(OCC)(=O)C>[ClH:1].[CH2:8]([O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C@H:17]([C:21]([NH:22][C:23]1[CH:28]=[C:27]([F:29])[C:26]([C:30]([CH3:35])([CH3:36])[CH2:31][O:32][CH2:33][CH3:34])=[C:25]([F:37])[CH:24]=1)=[O:38])[NH:16][CH2:15][CH2:14]2)[CH3:9]

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 131735747tert-butyl (R)-6-ethoxy-1-((4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 118622710(R)-6-ethoxy-N-(4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide hydrochlorideYield 97%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4N Hydrogen chloride/ethyl acetate (4 mL) was added to a solution of tert-butyl (R)-6-ethoxy-1-((4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (320 mg, 0.60 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)-6-ethoxy-N-(4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide hydrochloride (273 mg, 0.582 mmol, 97%) 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-ce14ef27223849b89d57a7b72f9fa8da
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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