Sulfur → Methyl 6-fluoroisoquinoline-3-carboxylate

HRID 409743Notes

Reaction equation

HRID 409743 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([F:15])[CH:12]=2)[CH2:7][NH:6]1)=[O:4].[S]>C1(C)C(C)=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([F:15])=[CH:10][CH:9]=2)=[O:4]

Participants

4

Reactant 2

HCID 5362487SulfurHCID 57947410Methyl 6-fluoro-1,2,3,4-tetrahydroisoquinoline-3-carboxylate

Product 1

HCID 57947434Methyl 6-fluoroisoquinoline-3-carboxylate

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 6-fluoro-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid methyl ester (92 g) and sulfur (42 g, 3 equiv.) in xylene (5 L) was stirred at 150° C. for 16 h. The reaction mixture was concentrated, and the resulting residue was dissolved in EtOAc, which was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure to give a crude mixture. Purification by flash column chromatography (hexanes/EtOAc, gradient 50%-100%) gave 6-fluoro-isoquinoline-3-carboxylic acid methyl ester as a light yellow solid (27 g, 24% for 3 steps). LRMS (M+H+) m/z 206.1.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe resulting residue was dissolved in EtOAc
  3. washwhich was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto give a crude mixture
  7. customPurification by flash column chromatography (hexanes/EtOAc, gradient 50%-100%)

Sources & evidence

ORD record
ord-47da2dd016714d7f8032cc6ff909fb02
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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