Acetic Acid → HCID 118075559, compound

HRID 1051638Notes

Reaction equation

HRID 1051638 reaction equation
N[C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[C:16]([Br:17])=[CH:15][CH:14]=[C:13]3[C:8]=2[CH2:9][CH2:10][C@H:11]([CH3:21])[N:12]3[C:18](=[O:20])[CH3:19])=[C:4]([F:24])[CH:3]=1.C(O)(=O)C.N([O-])=O.[Na+].S(=O)(O)[O-].[Na+]>C(O)C>[Br:17][C:16]1[C:7]([O:6][C:5]2[CH:22]=[CH:23][CH:2]=[CH:3][C:4]=2[F:24])=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]([C:18](=[O:20])[CH3:19])[C@@H:11]([CH3:21])[CH2:10][CH2:9]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 23665763Sodium BisulfiteHCID 23668193Sodium NitriteHCID 118076414HCID 118076414, compound

Product 1

HCID 118075559HCID 118075559, compoundYield 86.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 100-mL round-bottom flask was charged with 1-[(2S)-5-(4-amino-2-fluorophenoxy)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-1-yl]ethan-1-one (370 mg, 0.92 mmol) and acetic acid (5 mL). Sodium nitrite (1.3 g, 18.8 mmol) was added in portions, and the mixture stirred at room temperature for 30 minutes. Sodium bisulfite (2.0 g, 18.8 mmol) and ethanol (5 mL) were added, and the resulting mixture stirred for 12 h at room temperature. The reaction mixture was concentrated under vacuum, diluted with dichloromethane, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified via column chromatography on silica gel (eluting with 5:1, ethyl acetate/petroleum ether) to afford 1-[(2S)-6-bromo-5-(2-fluorophenoxy)-2-methyl-1,2,3,4-tetrahydroquinolin-1-yl]ethan-1-one (300 mg, 86%) of as yellow oil. MS (ESI, pos. ion) m/z 378, 380 [M+H]+.

Workup

  1. stirringthe resulting mixture stirred for 12 h at room temperature
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. additiondiluted with dichloromethane
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified via column chromatography on silica gel (eluting with 5:1, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-00891615a1ae419d81be85897871c892
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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