Formaldehyde → 2-Benzyl-2-aza-spiro[4.5]decane-4,4-dicarboxylic acid dimethyl ester hydrochloride

HRID 429531Notes

Reaction equation

HRID 429531 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4](=[C:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[C:5]([O:7][CH3:8])=[O:6].[ClH:16].[CH2:17]([NH:24][CH2:25]C(O)=O)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH2:29](N(CC)CC)C.C=O>C1C=CC=CC=1.C1(C)C=CC=CC=1>[ClH:16].[CH3:8][O:7][C:5]([C:4]1([C:3]([O:2][CH3:1])=[O:15])[C:9]2([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)[CH2:25][N:24]([CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:29]1)=[O:6]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 2756624N-Benzylglycine HydrochlorideHCID 132991472-Cyclohexylidene-malonic acid dimethyl ester

Product 1

HCID 99298522-Benzyl-2-aza-spiro[4.5]decane-4,4-dicarboxylic acid dimethyl ester hydrochlorideYield 22.1%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 1140TolueneSolvent

Procedure

A solution of dimethyl (cyclohexylidene) malonate 2 (594 mg; 2.8 mmol), N-benzylglycine hydrochloride (1.41 g; 6.99 mmol), triethylamine (0.97 mL; 6.95 mmol), and paraformaldehyde (671 mg; 22.36 mmol) in benzene (18 mL) was slowly heated up to 125° C. (oil bath) (Dean-Stark). After stirring for 2 hours, the reaction mixture was cooled to room temperature, diluted with toluene (20 mL), and washed with brine. The aqueous phase was extracted with toluene (2×10 mL). The organic phases were combined, dried over MgSO4, and evaporated to give a brown oil which was purified on silica gel chromatography (EtOAc/heptane 1:3). The resulting pale yellow oil was diluted in diethyl ether (10 mL), and the compound was extracted with 2N HCl (2×5 mL). The aqueous phases were combined, washed with diethyl ether, and concentrated in vacuo to give 3 as a white solid (238 mg; 0.62 mmol; 22%).

Workup

  1. washwashed with brine
  2. extractionThe aqueous phase was extracted with toluene (2×10 mL)
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customto give a brown oil which
  6. customwas purified on silica gel chromatography (EtOAc/heptane 1:3)
  7. additionThe resulting pale yellow oil was diluted in diethyl ether (10 mL)
  8. extractionthe compound was extracted with 2N HCl (2×5 mL)
  9. washwashed with diethyl ether
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-23d9a55fc90847a0a5295fb14ec056d1
Source dataset
uspto-grants-2001_11
Patent number
US06316638B1

Reaction notes

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