5-Cyclobutoxy-7,8-difluoro-2-methylquinoline → (S)-5-cyclobutoxy-7,8-difluoro-2-methyl-1,2,3,4-tetrahydroquinoline

HRID 1051582Notes

Reaction equation

HRID 1051582 reaction equation
[CH:1]1([O:5][C:6]2[CH:15]=[C:14]([F:16])[C:13]([F:17])=[C:12]3[C:7]=2[CH:8]=[CH:9][C:10]([CH3:18])=[N:11]3)[CH2:4][CH2:3][CH2:2]1.[H][H]>CO>[CH:1]1([O:5][C:6]2[CH:15]=[C:14]([F:16])[C:13]([F:17])=[C:12]3[C:7]=2[CH2:8][CH2:9][C@H:10]([CH3:18])[NH:11]3)[CH2:2][CH2:3][CH2:4]1

Participants

4

Reactant 2

HCID 1180757225-Cyclobutoxy-7,8-difluoro-2-methylquinolineHCID 178418361HCID 178418361, compound3×

Product 1

HCID 118075503(S)-5-cyclobutoxy-7,8-difluoro-2-methyl-1,2,3,4-tetrahydroquinolineYield 33%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 30-mL glass-lined stainless steel reactor was charged with 5-cyclobutoxy-7,8-difluoro-2-methylquinoline (4.2 g, 16.9 mmol), Cp*Ru(OTf)[(S,S)-TsDPEN](0.100 g, 0.13 mmol) and methanol (10 mL). The reactor was closed and hydrogen was introduced in at a pressure of 50 atm, before being reduced to 1 atm. After this procedure was repeated three times, the reactor was pressurized with hydrogen to 50 atm. The resulting mixture was stirred under this hydrogen pressure for 24 h at room temperature. After carefully releasing the hydrogen, the reaction mixture was concentrated under vacuum. The residue purified via column chromatography on silica gel (eluting with 25% ethyl acetate/petroleum ether) to afford (S)-5-cyclobutoxy-7,8-difluoro-2-methyl-1,2,3,4-tetrahydroquinoline (1.4 g, 33%, 87% ee) as colorless oil.

Workup

  1. customThe reactor was closed
  2. concentrationthe reaction mixture was concentrated under vacuum
  3. customThe residue purified via column chromatography on silica gel (eluting with 25% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-05a9c88ffac24ddfa9d51d9e0327198a
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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