Diazomethane → 6-(tert-butoxycarbonyl)-6-azaspiro[2.5]octane-5(S)-carboxylic acid benzyl ester

HRID 536582Notes

Reaction equation

HRID 536582 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH2:14])[CH2:10][C@H:9]1[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+](=[CH2:27])=[N-]>C1COCC1.CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2([CH2:27][CH2:14]2)[CH2:10][C@H:9]1[C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 9550DiazomethaneHCID 668487244-methylene-1-(tert-butoxycarbonyl)piperidine-2(S)-carboxylic acid benzyl ester2×

Product 1

HCID 668483686-(tert-butoxycarbonyl)-6-azaspiro[2.5]octane-5(S)-carboxylic acid benzyl esterYield 88%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-4-methylene-piperidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (intermediate 15 prepared by Method A, 120 g, 0.36 mol) in anhydrous THF (1 L) was added diazomethane in ether (500 ml) [which was prepared from methyl-3-nitro-1-nitroxoguanide (213 g) in 40% KOH (1 L)] at −25° C. to −35° C. slowly under the protection of nitrogen and warmed to room temperature slowly (about 4 hours) and stirred at room temperature for 10 hours. The mixture is filtered and the liquid phase was evaporated to obtain a crude that was purified by silica gel chromatography (petroleum ether/ethyl acetate from 10/1 to 5/1). (S)-6-Aza-spiro[2.5]octane-5,6-dicarboxylic acid 5-benzyl ester 6-tert-butyl ester was obtained as colourless oil (110 g), yield:88%.

Workup

  1. filtrationThe mixture is filtered
  2. customthe liquid phase was evaporated
  3. customto obtain a crude that
  4. customwas purified by silica gel chromatography (petroleum ether/ethyl acetate from 10/1 to 5/1)

Sources & evidence

ORD record
ord-ff08b30816834a1aa2c3edf551fe5a1f
Source dataset
uspto-grants-2014_10
Patent number
US08859608B2

Reaction notes

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