Formaldehyde → tert-Butyl (3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrole-1(2H)-carboxylate

HRID 1947384

Reaction equation

HRID 1947384 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]2[CH2:13][NH:14][CH2:15][C@H:9]12)=[O:7])([CH3:4])([CH3:3])[CH3:2].C=O.[C:18]([BH3-])#N.[Na+]>CO.[OH-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]2[CH2:13][N:14]([CH3:18])[CH2:15][C@H:9]12)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 29949076rac-tert-butyl (3aR,6aR)-octahydropyrrolo(2,3-c)pyrrole-1-carboxylate

Product 1

HCID 44221715tert-Butyl (3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrole-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of (3aR,6aR)-hexahydro-pyrrolo[3,4-b]pyrrole-1-carboxylic acid tert-butyl ester (18.31 g, 0.86 mol) in methanol (450 ml) was added paraformaldehyde (52 g, 1.72 mole) and the mixture was stirred at room temperature for 1 hour. Sodium cyanoborohydride was then added and the mixture was stirred at room temperature for 10 hours, diluted with 1N NaOH (450 ml), extracted with dichloromethane (5×200 ml). The combined organic layers were dried (Na2SO4), filtered and concentrated to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 4.18 (m, 1H) 3.47-3.59 (m, 1H) 3.34-3.46 (m, 2H) 2.75-2.90 (m, 1H) 2.71 (m, 1H) 2.44-2.60 (m, 2H) 2.29 (s, 3H) 1.89-2.06 (m, 1H) 1.65-1.81 (m, 1H) 1.42-1.49 (m, 9H). MS: (M+H)+=226.

Workup

  1. stirringthe mixture was stirred at room temperature for 10 hours
  2. extractionextracted with dichloromethane (5×200 ml)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5331af3b36f84ff4a03c49ece522de82
Source dataset
uspto-grants-2013_03
Patent number
US08399468B2

Linked notes

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