Hydrochloric Acid → (2S,4S)-N-acetyl-4-azido-2-hydroxymethylpyrrolidine

HRID 1723902Notes

Reaction equation

HRID 1723902 reaction equation
C([O:3][C:4](=O)[C@@H:5]1[CH2:9][CH:8]([N:10]=[N+:11]=[N-:12])[CH2:7][N:6]1[C:13](=[O:15])[CH3:14])C.[BH4-].[Na+].Cl>C(O)C.C(=O)(O)[O-].[Na+]>[C:13]([N:6]1[CH2:7][C@@H:8]([N:10]=[N+:11]=[N-:12])[CH2:9][C@H:5]1[CH2:4][OH:3])(=[O:15])[CH3:14]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 86601301N-acetyl-4-azido-L-proline ethyl ester

Product 1

HCID 86601302(2S,4S)-N-acetyl-4-azido-2-hydroxymethylpyrrolidineYield 101.8%

Reagents, catalysts & solvents 2

HCID 516892Sodium BicarbonateCatalystHCID 702EthanolSolvent2×

Procedure

644 g of N-acetyl-4-azido-L-proline ethyl ester dissolved in 700 ml of ethanol was added dropwise to a suspension of 2.5 L of ethanol and 162 g of sodium borohydride at not higher than 10° C. while cooling. After overnight reaction, 35% hydrochloric acid (594 g) was added dropwise to the above mixture at not higher than 20° C. while cooling, and the solution was neutralized with sodium bicarbonate (24 g). After filtration, the solution was concentrated under reduced pressure while the solvent was substituted with 1.3 L of isopropyl alcohol, thereby to obtain 534 g of (2S,4S)-N-acetyl-4-azido-2-hydroxymethylpyrrolidine as an oil.

Workup

  1. temperaturewhile cooling
  2. additionwas added dropwise to the above mixture at not higher than 20° C.
  3. temperaturewhile cooling
  4. filtrationAfter filtration
  5. concentrationthe solution was concentrated under reduced pressure while the solvent

Sources & evidence

ORD record
ord-30983ad5fe964d3393581460f94dec0b
Source dataset
uspto-grants-2009_02
Patent number
US07485665B2

Reaction notes

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