Tert-butyl 3-(benzyloxycarbonylamino)-4-hydroxy-pyrrolidine-1-carboxylate → 1-Methyl-4-(methylamino)pyrrolidin-3-OL

HRID 503712Notes

Reaction equation

HRID 503712 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].C(O[C:12]([N:14]1[CH2:18][CH:17]([OH:19])[CH:16]([NH:20][C:21](OCC2C=CC=CC=2)=O)[CH2:15]1)=O)(C)(C)C>C1COCC1>[CH3:12][N:14]1[CH2:15][CH:16]([NH:20][CH3:21])[CH:17]([OH:19])[CH2:18]1

Participants

4

Reactant 2

HCID 20691380Tert-butyl 3-(benzyloxycarbonylamino)-4-hydroxy-pyrrolidine-1-carboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 684650761-Methyl-4-(methylamino)pyrrolidin-3-OLYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

LAH (1.40 g, 35.0 mmol) is slowly added to a stirred solution of 3-benzyloxycarbonylamino-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester in THF (15 ml) at room temperature. The reaction mixture is heated to reflux under N2 for 2 hours and then cooled to 0° C. The reaction mixture is quenched by the slow addition of Na2SO4.10H2O, warmed to room temperature, diluted with ethyl acetate and filtered through Celite. The filtrate is concentrated and purified on a silica gel column (10:1:0.5 methylene chloride, MeOH, 30% NH4OH solution) to yield 0.21 g (18% for two steps) 1-methyl-4-methylamino-pyrrolidin-3-ol.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux under N2 for 2 hours
  3. customThe reaction mixture is quenched by the slow addition of Na2SO4.10H2O
  4. temperaturewarmed to room temperature
  5. additiondiluted with ethyl acetate
  6. filtrationfiltered through Celite
  7. concentrationThe filtrate is concentrated
  8. custompurified on a silica gel column (10:1:0.5 methylene chloride, MeOH, 30% NH4OH solution)

Sources & evidence

ORD record
ord-75f538ad411d4e8195ad4154eeeddb91
Source dataset
uspto-grants-2010_08
Patent number
US07777032B2

Reaction notes

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