Acetyl chloride → 6-Acetyl-5,6,7,8-tetrahydro-1,6-naphthyridine

HRID 1003993Notes

Reaction equation

HRID 1003993 reaction equation
[N:1]1[C:10]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:18](Cl)(=[O:20])[CH3:19]>ClCCl>[C:18]([N:7]1[CH2:8][CH2:9][C:10]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]=2[CH2:6]1)(=[O:20])[CH3:19]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 131938825,6,7,8-Tetrahydro-1,6-naphthyridine

Product 1

HCID 187651916-Acetyl-5,6,7,8-tetrahydro-1,6-naphthyridineYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5,6,7,8-tetrahydro-1,6-naphthyridine [Shiozawa et al Chem. Pharm. Bull., 32, 2522 (1984)] (4.9 g, 0.037 mol) in dichloromethane at 0° C. was added triethylamine (6.1 ml, 0.044 mol) and acetyl chloride (3.11 ml, 0.044 mol) dropwise and the reaction was allowed to warm to room temperature and stirred for a further 18 hours. The reaction mixture was partitioned between water and dichloromethane, the layers were separated and the aqueous layer was extracted twice more with dichloromethane. The combined organic layers were dried over MgSO4 and evaporated under reduced pressure to afford a residue which was purified on silica gel, eluting with 0.880 aqueous ammonia:methanol:dichloromethane (0.5:3.5:96, v/v). This afforded the title compound (58%) as an oil. Rf 0.60 (0.880 aqueous ammonia:methanol:dichloromethane, 2:14:84, v/v). 1H NMR (CDCl3): δ=2.15 (3H, s), 3.04 (2H, m), 3.75 and 3.90 (2H, 2×m), 4.60 and 4.70 (2H, 2×s), 7.10 (1H, m), 7.42 (1H, m), 8.42 (1H, m).

Workup

  1. customThe reaction mixture was partitioned between water and dichloromethane
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted twice more with dichloromethane
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. customevaporated under reduced pressure
  6. customto afford a residue which
  7. customwas purified on silica gel
  8. washeluting with 0.880 aqueous ammonia:methanol:dichloromethane (0.5:3.5:96

Sources & evidence

ORD record
ord-1bf77b401baf43c5add0b06391b7b3c0
Source dataset
uspto-grants-2000_04
Patent number
US06048864

Reaction notes

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