Thionyl Chloride → N-(3-Methyl-5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)acetamide

HRID 718811Notes

Reaction equation

HRID 718811 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[C:7]([C:12](=O)[CH2:13][CH2:14][C:15]([OH:17])=O)[CH:8]=[CH:9][C:10]=1[CH3:11])(=[O:3])[CH3:2].S(Cl)(Cl)=O.[Al+3].[Cl-].[Cl-].[Cl-]>[N+](C)([O-])=O>[CH3:11][C:10]1[C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:6][C:7]2[CH2:12][CH2:13][CH2:14][C:15](=[O:17])[C:8]=2[CH:9]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 6451240Aluminum(III) ChlorideHCID 867224214-(3-Acetamido-4-methylphenyl)-4-oxobutanoic acid

Product 1

HCID 20222994N-(3-Methyl-5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)acetamideYield 65%

Reagents, catalysts & solvents 1

HCID 6375NitromethaneSolvent

Procedure

In a mechanically stirred 50 L vessel, 4-(3-acetamido-4-methylphenyl)-4-oxobutanoic acid (74) (675 g, 2.87 mol) was dissolved in nitromethane (13.75 L). Thionyl chloride (255 mL, 3.49 mol) was added. The resulting mixture was stirred for about 1.5 h at rt. AlCl3 (973 g, 7.30 mol) was added maintaining a temperature of about 25° C. The resulting mixture was stirred for another about 30 min and then poured onto ice water (30 L). The resulting mixture was extracted with EtOAc (1×60 L then 2×20 L). The organic layers were combined and washed with sat. aq. NaCl (1×10 L), 1 M aq. NaOH (15 L) and sat. aq. NaCl (1×10 L). The organic layer was dried over Na2SO4, filtered, and concentrated to afford N-(3-Methyl-5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)acetamide (380 g, 65% yield). 1H NMR (300 MHz, DMSO): δ 9.36 (s, 1H), 7.68 (s, 1H), 7.62 (s, 1H), 2.86 (m, 2H), 2.55 (m, 2H), 2.23 (s, 3H), 2.06 (s, 3H), 2.00 (m, 2H).

Workup

  1. temperaturemaintaining a temperature of about 25° C
  2. stirringThe resulting mixture was stirred for another about 30 min
  3. additionpoured onto ice water (30 L)
  4. extractionThe resulting mixture was extracted with EtOAc (1×60 L
  5. washwashed with sat. aq. NaCl (1×10 L), 1 M aq. NaOH (15 L) and sat. aq. NaCl (1×10 L)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-15a32b4ddaff43659bfd88eb547eabba
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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