Diethyl Ether → tert-butyl (2S)-2-(hydroxymethyl)-4-methylidenepyrrolidine-1-carboxylate

HRID 458388Notes

Reaction equation

HRID 458388 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[CH2:13])[CH2:10][C@H:9]1[C:14](O)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.[BH4-].[Na+].CCOCC>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[CH2:13])[CH2:10][C@H:9]1[CH2:14][OH:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 79724-MethylmorpholineHCID 4311764Sodium borohydrideHCID 21727417(2S)-1-((tert-butoxy)carbonyl)-4-methylidenepyrrolidine-2-carboxylic acid

Product 1

HCID 66733597tert-butyl (2S)-2-(hydroxymethyl)-4-methylidenepyrrolidine-1-carboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 14.7 g (64.7 mmol) (2S)-4-Methylene-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester in 80 ml THF were added 7.13 ml (64.7 mmol, 1.0 eq) N-methylmorpholine and 8.5 ml (64.0 mmol, 1.0 eq) isobutylchloro formate at −5° C. and the solution was stirred at that temperature for 1.5 h. The mixture was filtered and added to a suspension of 3.7 g (97.8 mmol, 1.5 eq) NaBH4 in 30 ml water over a period of 25 min at 0° C. The reaction was stirred at 0° C. for 2 h and at RT over night. Ether was added, the layers were separated and the inorganic layer was extracted with ether and CH2Cl2, the organic layers were washed with brine, dried over Na2SO4, filtered and evaporated, yielding 9.3 g (68%) (2S)-2-Hydroxymethyl-4-methylene-pyrrolidine-1-carboxylic acid tert-butyl ester as light brown oil, MS: 182 (M-CH2OH.).

Workup

  1. filtrationThe mixture was filtered
  2. stirringThe reaction was stirred at 0° C. for 2 h and at RT over night
  3. customthe layers were separated
  4. extractionthe inorganic layer was extracted with ether and CH2Cl2
  5. washthe organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-8db6a48204e44ab1854e6fa107429912
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

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