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

HRID 1006858Notes

Reaction equation

HRID 1006858 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-b833e40dbfbf4e30ac1cfeca5cae1c7c
Source dataset
uspto-grants-2004_09
Patent number
US06790860B2

Reaction notes

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