Acetic Acid → tert-Butyl (2S)-2-[(dimethylamino)methyl]pyrrolidine-1-carboxylate

HRID 2104331Notes

Reaction equation

HRID 2104331 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:9]1[CH:10]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:15][NH:16][CH3:17].C(O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:9]1[CH2:10][N:16]([CH3:17])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 674DimethylamineHCID 702EthanolHCID 2734674tert-butyl (2S)-2-formylpyrrolidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 60017963tert-Butyl (2S)-2-[(dimethylamino)methyl]pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Crude N-t-butyloxycarbonyl-(S)-prolinal (2.34 g, 11.7 mmol) was dissolved in dichloromethane (90 ml). A 5.6 M solution of dimethylamine in ethanol (4.19 ml, 23.5 mmol) was added. 0.4 nm Mol sieves (10.0 g) was added. Sodium triacetoxyborohydride 7.47 g, 35.2 mmol) and glacial acetic acid (1.34 ml, 23.5 mmol) were added successively. The reaction mixture was stirred for 3 days. It was filtered through a plug of celite. The celite was washed with methanol (150 ml). An 1N aqueous solution of sodium hydroxide (150 ml) and tert-butyl methyl ether (150 ml) were added. The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (3×100 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (90 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent, to give 1.29 g of (2S)-2-((dimethylamino)methyl)pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. addition0.4 nm Mol sieves (10.0 g) was added
  2. filtrationIt was filtered through a plug of celite
  3. washThe celite was washed with methanol (150 ml)
  4. additionAn 1N aqueous solution of sodium hydroxide (150 ml) and tert-butyl methyl ether (150 ml) were added
  5. customThe phases were separated
  6. extractionThe aqueous phase was extracted with tert-butyl methyl ether (3×100 ml)
  7. dry with materialThe combined organic layers were dried over magnesium sulfate
  8. customThe solvent was removed in vacuo
  9. customThe crude product was purified by flash chromatography on silica (90 g)

Sources & evidence

ORD record
ord-dc0c83280b524a3cad298c5626f1f96d
Source dataset
uspto-grants-2009_08
Patent number
US07576062B2

Reaction notes

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