Acetyl chloride → Cyclohexanone

HRID 429533Notes

Reaction equation

HRID 429533 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].Cl.[CH3:6][O:7][C:8]([C:10]1(C(OC)=O)[C:14]2([CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[CH2:13][N:12]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:11]1)=[O:9]>CO>[C:1]1(=[O:3])[CH2:13][CH2:14][CH2:10][CH2:8][CH2:2]1.[CH3:6][O:7][C:8]([CH:10]1[C:14]2([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]2)[CH2:13][N:12]([CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:11]1)=[O:9]

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 99298522-Benzyl-2-aza-spiro[4.5]decane-4,4-dicarboxylic acid dimethyl ester hydrochloride

Product 2

HCID 7967CyclohexanoneHCID 120428242-Benzyl-2-aza-spiro[4.5]decane-4-carboxylic Acid Methyl Ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (1) (4 g; 20.70 mmol), N-benzylglycine hydrochloride (10.4 g; 51.57 mmol), triethylamine (7.2 mL; 51.65 mmol), and paraformaldehyde (5.2 g; 173.30 mmol) in benzene (120 mL) was refluxed for 2 hours using a Dean-Stark apparatus. After cooling, the reaction mixture was diluted with toluene (200 mL) and washed with brine. The aqueous phase was extracted with toluene (3×30 mL). The organic extracts were combined, dried over MgSO4, and concentrated in vacuo. The crude oil was purified over silica-gel chromatography in EtOAc/heptane (1:3) to give a yellow oil which was diluted in ether (30 mL) and extracted with 3N HCl (3×25 mL). The aqueous phase was washed with ether (2×30 mL) and was concentrated under vacuum to give (2) as a white powder (6.20 g; 17.08 mmol) which was used without any further purification. A solution of (2) (6.2 g; 17.08 mmol) in 6N HCl (120 mL) was refluxed overnight. Evaporating the solvent in vacuo gave 5 g (16.13 mmol; 77% from (1)) of (3) as a pale yellow solid which was immediately esterified. Acetyl chloride (5 mL; 70.32 mmol) was slowly added to methanol (100 mL), at 0° C., under an argon atmosphere. After stirring for 10 minutes, this solution was transferred to a flask containing (3) (5 g; 16.13 mmol), under an argon atmosphere. The reaction mixture was then stirred at 95° C. for 3 hours. After cooling, the methanol was removed in vacuo. The residue was basified with saturated aqueous Na2CO3, and was extracted with ether (3×30 mL). The organic phases were combined, dried over MgSO4, and concentrated to give 3 g (10.44 mmol; 50% from (1)) of (4) as a pale yellow liquid.

Workup

  1. customthis solution was transferred to a flask
  2. stirringThe reaction mixture was then stirred at 95° C. for 3 hours
  3. temperatureAfter cooling
  4. customthe methanol was removed in vacuo
  5. extractionwas extracted with ether (3×30 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d2f2b34b6a654a29876069a1f5f86009
Source dataset
uspto-grants-2001_11
Patent number
US06316638B1

Reaction notes

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