tert-butyl 2-(3-((R)-1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutylidene)acetate → tert-butyl (R)-2-(3-(1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutyl)acetate

HRID 2202216Notes

Reaction equation

HRID 2202216 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]([C@H:16]2[C:25]3[C:20](=[CH:21][C:22]([O:26][CH3:27])=[CH:23][CH:24]=3)[CH2:19][CH2:18][N:17]2[C:28]([CH:30]2[CH2:33][C:32](=[CH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]2)=[O:29])=[O:15])[CH:5]=[C:6]([F:12])[C:7]=1[Si:8]([CH3:11])([CH3:10])[CH3:9]>CO.[C].[Pd]>[F:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]([C@H:16]2[C:25]3[C:20](=[CH:21][C:22]([O:26][CH3:27])=[CH:23][CH:24]=3)[CH2:19][CH2:18][N:17]2[C:28]([CH:30]2[CH2:31][CH:32]([CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:33]2)=[O:29])=[O:15])[CH:5]=[C:6]([F:12])[C:7]=1[Si:8]([CH3:9])([CH3:11])[CH3:10]

Participants

4

Reactant 1

HCID 131735728tert-butyl 2-(3-((R)-1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutylidene)acetate

Product 1

HCID 131735729tert-butyl (R)-2-(3-(1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutyl)acetateYield 85%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolvent

Procedure

A mixture of tert-butyl 2-(3-((R)-1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutylidene)acetate (138 mg, 0.24 mmol) and 10% palladium-carbon (25.1 mg, 0.24 mmol, 50%, wet) in MeOH (20 mL) was stirred overnight at room temperature under hydrogen atmosphere (1 atm). The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 5→50% ethyl acetate/hexane) to give tert-butyl (R)-2-(3-(1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutyl)acetate (118 mg, 0.201 mmol, 85%) as a colorless oil.

Workup

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 5→50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e1683ace01984e0aab5301d3f1b4e130
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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