Diethyl Ether → tert-Butyl 3-hydroxy-3-methylpyrrolidine-1-carboxylate

HRID 1496704Notes

Reaction equation

HRID 1496704 reaction equation
[Li+].[Cl-].C[Mg+].[Br-].[CH2:6](OCC)C.[O:11]=[C:12]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]1.[NH4+].[Cl-]>C1COCC1.[Cl-].[Cl-].[Zn+2]>[OH:11][C:12]1([CH3:6])[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]1

Participants

8

Reactant 5

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 178418689HCID 178418689, compound

Product 1

HCID 22951485tert-Butyl 3-hydroxy-3-methylpyrrolidine-1-carboxylateYield 83.8%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a 30 L reaction kettle was added 4 L dry THF at −10° C. After stirring, to the mixture were added ZnCl2 (118 g, 0.86 mol) and LiCl (402 g, 9.5 mol). After half an hour, to the resulting mixture was slowly added dropwisely a solution of MeMgBr (3 mol/L) in diethyl ether (6.4 L, 19.2 mol). The stirring was continued for half an hour. To the resulting mixture was slowly added a solution of tert-butyl 3-oxopyrrolidine-1-carboxylate (1600 g, 8.6 mol) in THF dropwisely. After the completion of reaction by HPLC detection, to the system was dropwisely added a saturated NH4Cl solution to quench off the reaction. The reaction was extracted with ethyl acetate. The organic phase was washed with a saturated aqueous NaCl solution, dried over anhydrous sodium sulfate, and evaporated to remove the solvent to produce tert-butyl 3-hydroxy-3-methylpyrrolidine-1-carboxylate as a pale-yellow solid (1450 g) in a yield of 83.8%.

Workup

  1. customTo a 30 L reaction kettle
  2. waitAfter half an hour
  3. waitThe stirring was continued for half an hour
  4. customAfter the completion of reaction by HPLC detection
  5. customto quench off
  6. customthe reaction
  7. extractionThe reaction was extracted with ethyl acetate
  8. washThe organic phase was washed with a saturated aqueous NaCl solution
  9. dry with materialdried over anhydrous sodium sulfate
  10. customevaporated
  11. customto remove the solvent

Sources & evidence

ORD record
ord-14c0b46b37a14884b22474ff11b6e748
Source dataset
uspto-grants-2015_12
Patent number
US09198902B2

Reaction notes

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