Diazomethane → Hexahydro-pyrrolo[3,2-b]pyrrole-1,3,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 3-methyl ester

HRID 1965205Notes

Reaction equation

HRID 1965205 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:15]2[CH:11]([N:12]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])[CH2:13][CH:14]2[C:16]([OH:18])=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+](=[CH2:31])=[N-].N(N(C)C(N)=O)=O.[OH-].[K+]>CCOC(C)=O.CCOCC>[CH3:31][O:17][C:16]([CH:14]1[CH2:13][N:12]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH:15]12)=[O:18]

Participants

7

Reactant 4

HCID 9550DiazomethaneHCID 12699N-Methyl-N-nitrosoureaHCID 14797Potassium HydroxideHCID 67216716Hexahydro-pyrrolo[3,2-b]pyrrole-1,3,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester

Product 1

HCID 67280928Hexahydro-pyrrolo[3,2-b]pyrrole-1,3,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 3-methyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of crude 72 (0.47 g) in EtOAc (10 mL) and Et2O (10 mL) was added an ethereal solution of diazomethane that was prepared by treatment of N-nitroso-N-methyl urea (0.5 g) in Et2O (10 mL) with 1M KOH (10 mL). After consumption of starting material (monitored by TLC), the reaction mixture was diluted with HOAc. The solution was extracted with EtOAc, washed with saturated NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated to give a dark oil that was purified by HPLC (2″ Dynamax® SiO2, 10% EtOAc/hexane to 100% EtOAc over 30 min) to give 76 (0.19 g) as a yellow-colored oil. 1H NMR (CDCl3, 300 MHz): δ7.40-7.29 (m, 5H), 5.23-5.09 (m, 2H), 4.56-4.52 (m, 2H), 4.11-4.04 (m, 1H), 3.69 (s, 3H), 3.45-3.42 (m, 1H), 3.22-3.12 (m, 1H), 2.27-2.10 (m, 1H), 1.96 (m, 1H), 1.47 (s, 9H) ppm. Mass spectrum, m/z [405.2] (M+H)+.

Workup

  1. customAfter consumption of starting material (monitored by TLC)
  2. additionthe reaction mixture was diluted with HOAc
  3. extractionThe solution was extracted with EtOAc
  4. washwashed with saturated NaHCO3, brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a dark oil that
  9. customwas purified by HPLC (2″ Dynamax® SiO2, 10% EtOAc/hexane to 100% EtOAc over 30 min)

Sources & evidence

ORD record
ord-e330af8497fa45398e5b42c0ec0e35e9
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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