Hydrochloric Acid → N-((3R,5S)-5-Hydroxymethyl-pyrrolidin-3-yl)-acetamide hydrochloride

HRID 1012018Notes

Reaction equation

HRID 1012018 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].CO[C:9]([C@@H:11]1[CH2:15][C@@H:14]([N:16]=[N+]=[N-])[CH2:13][N:12]1C(OC(C)(C)C)=O)=[O:10].C(=O)([O-])[O-].[Na+].[Na+].[C:32](OC(=O)C)(=[O:34])[CH3:33].[ClH:39]>C1COCC1.O1CCOCC1.O>[ClH:39].[OH:10][CH2:9][C@H:11]1[NH:12][CH2:13][C@H:14]([NH:16][C:32](=[O:34])[CH3:33])[CH2:15]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 10340Sodium CarbonateHCID 11369242(2S,4R)-4-Azido-1,2-pyrrolidinedicarboxylic Acid 1-(1,1-Dimethylethyl) 2-Methyl EsterHCID 21226445Aluminium lithium hydride

Product 1

HCID 66901605N-((3R,5S)-5-Hydroxymethyl-pyrrolidin-3-yl)-acetamide hydrochlorideYield 80%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To an ice-cold suspension of lithium aluminium hydride (0.6 g, 15 mmol) in THF (10 ml) was added a solution of (2S,4R)-4-azido-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.0 g, 4 mmol) in THF (5 mL) and the mixture stirred for 1 h. Water was then cautiously added to the reaction and the mixture filtered and concentrated. The residue was then taken up in CH2Cl2 (10 ml) and saturated sodium carbonate (10 ml) and acetic anhydride (0.3 ml, 3 mmol) added. The mixture was stirred for 2 h after which time the organic was collected, dried (Na2SO4) and concentrated. The residue (0.6 g, 2 mmol) was then treated with 4 M hydrochloric acid in dioxane (5 ml) for 1 h, evaporation of the solvent afforded the title compound (0.5 g, 80%) as a yellow solid. MS: 159.1 (MH+).

Workup

  1. filtrationthe mixture filtered
  2. concentrationconcentrated
  3. stirringThe mixture was stirred for 2 h after which time the
  4. customorganic was collected
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customevaporation of the solvent

Sources & evidence

ORD record
ord-ebf22027614840a7862850e9751d0736
Source dataset
uspto-grants-2011_07
Patent number
US07977358B2

Reaction notes

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