Water → Tert-butyl 3-((cyclopropylmethoxy)methyl)pyrrolidine-1-carboxylate

HRID 1808222Notes

Reaction equation

HRID 1808222 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]1.[H-].[Na+].Cl[CH2:18][CH:19]1[CH2:21][CH2:20]1.O>CN(C)C=O.C1COCC1>[CH:19]1([CH2:18][O:1][CH2:2][CH:3]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]2)[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 80013(Chloromethyl)cyclopropaneHCID 5237175tert-Butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 57732113Tert-butyl 3-((cyclopropylmethoxy)methyl)pyrrolidine-1-carboxylateYield 84.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate (Preparation 65, 46.6 g, 0.232 mol, 1 eq) in anhydrous dimethylformamide (250 mL) was added in portions with stirring and under an atmosphere of argon a dispersion in oil of sodium hydride (11.2 g, 0.28 mol, 1.2 eq) in oil. The mixture was stirred for 45 min and then (chloromethyl)cyclopropane (26 mL, 0.28 mol, 1.2 eq) in anhydrous THF (30 mL) was added. The mixture was stirred for 12 h and then treated with water (100 mL) and extracted with ether (3×200 mL). Ether fractions were washed with water (2×100 mL), dried over sodium sulfate and evaporated. The residue was subjected to chromatography (chloroform/ethylacetate 10:1) on silica to afford title compound (50 g, 0.195 mol, 84%).

Workup

  1. stirringThe mixture was stirred for 12 h
  2. extractionextracted with ether (3×200 mL)
  3. washEther fractions were washed with water (2×100 mL)
  4. dry with materialdried over sodium sulfate
  5. customevaporated

Sources & evidence

ORD record
ord-f6de50b82eaf4305bc5336ad45a196a3
Source dataset
uspto-grants-2013_01
Patent number
US08357711B2

Reaction notes

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