Pyridine → 2-Aza-spiro[4.5]decane-2,4-dicarboxylic acid 2-benzyl ester 4-methyl ester

HRID 2296776Notes

Reaction equation

HRID 2296776 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[C:9]2([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH2:8][N:7](CC2C=CC=CC=2)[CH2:6]1)=[O:4].[H][H].Cl.C1C2(CCCCC2)C(C(O)=O)CN1.N1C=CC=CC=1.[CH2:44]([O:51][C:52](Cl)=[O:53])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>CO.ClCCl>[CH3:1][O:2][C:3]([CH:5]1[C:9]2([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH2:8][N:7]([C:52]([O:51][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:53])[CH2:6]1)=[O:4]

Participants

8

Reactant 5

HCID 1049PyridineHCID 10387Benzyl chloroformateHCID 98158602-Azaspiro[4.5]decane-4-carboxylic acid hydrochlorideHCID 120428242-Benzyl-2-aza-spiro[4.5]decane-4-carboxylic Acid Methyl EsterHCID 178418361HCID 178418361, compound

Product 1

HCID 120428262-Aza-spiro[4.5]decane-2,4-dicarboxylic acid 2-benzyl ester 4-methyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (4) (3 g; 10.44 mmol) and 10% Pd (OH)2/C (0.60 g; 20% w/w) in methanol (50 mL) was stirred for 24 hours at 40° C. under at atmosphere of dry hydrogen gas. The catalyst was filtered off through a celite pad, and the filtrate was concentrated in vacuo to.give 2 g (10.14 mmol; 97%) of (5) as a colorless oil which was used without any further purification. To a solution of (5) (2 g; 10.14 mmol) in dry dichloromethane (100 mL) was successively added, at 0° C., under an argon atmosphere, pyridine (2.04 mL; 25.35 mmol), and benzylchloroformate (2.89 mL; 20.24 mmol). The reaction mixture was then allowed to stir at room temperature for 2 days. The reaction mixture was washed (2×50 mL) with IN HCl, dried over MgSO4, and concentrated in vacuo. The crude oil was purified by silica-gel flash chromatography in ether/heptane (1:1) to give 2.97 g (8.96 mmol; 88%) of (6) as a colorless oil.

Workup

  1. filtrationThe catalyst was filtered off through a celite pad
  2. concentrationthe filtrate was concentrated in vacuo to.give 2 g (10.14 mmol; 97%) of (5) as a colorless oil which
  3. customwas used without any further purification
  4. washThe reaction mixture was washed (2×50 mL) with IN HCl
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude oil was purified by silica-gel flash chromatography in ether/heptane (1:1)

Sources & evidence

ORD record
ord-6d72ee0b26e5419c84dc179866403fd0
Source dataset
uspto-grants-2002_12
Patent number
US06489352B2

Reaction notes

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