Ammonium Chloride → 2-(R)-(2-(S)-Dibenzylamino-1-(S)-hydroxy-3-phenylpropyl)-5,5-dimethylpyrrolidine-1-carboxylic acid tert-butyl ester

HRID 732374Notes

Reaction equation

HRID 732374 reaction equation
C([Li])(CC)C.C1C[C@H]2N(C[C@H]3[C@@H]4CCCCN4C[C@@H]2C3)CC1.[C:23]([O:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C:31]1([CH3:36])[CH3:35])=[O:29])([CH3:26])([CH3:25])[CH3:24].[CH2:37]([N:44]([CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C@@H:45]([CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[CH:46]=[O:47])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[Cl-].[NH4+]>C(OCC)C.C(OCC)(=O)C>[C:23]([O:27][C:28]([N:30]1[C:31]([CH3:36])([CH3:35])[CH2:32][CH2:33][C@@H:34]1[C@@H:46]([OH:47])[C@@H:45]([N:44]([CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[CH2:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 644020SparteineHCID 9883943(alphaS)-alpha-[Bis(phenylmethyl)amino]benzenepropanalHCID 57366408tert-Butyl 2,2-dimethylpyrrolidine-1-carboxylateHCID 178418400CID 53628100

Product 1

HCID 688152432-(R)-(2-(S)-Dibenzylamino-1-(S)-hydroxy-3-phenylpropyl)-5,5-dimethylpyrrolidine-1-carboxylic acid tert-butyl esterYield 12%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

Add sec-butyllithium (2.9 mL, 2.1 mmol) dropwise to a solution of freshly distilled (−)-sparteine (1 mL, 4.3 mmol) in diethyl ether (25 mL) over 3 min at −78° C. Add 2,2-dimethylpyrrolidine-1-carboxylic acid tert-butyl ester (645 mg, 3.2 mmol) in diethyl ether (2 mL) dropwise over 10 min. Stir 2 h, add 2-(S)-dibenzylamino-3-phenylpropionaldehyde (967 mg, 2.9 mmol) in diethyl ether (2 mL) over 5 min and stir 20 min. Add saturated aqueous ammonium chloride solution and ethyl acetate and let warm to room temperature, separate the layers, extract the aqueous layer with ethyl acetate, wash the organic layer with saturated aqueous sodium chloride solution, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate) to give the title compound as a colorless oil (182 mg, 12%).

Workup

  1. stirringstir 20 min
  2. customseparate the layers
  3. extractionextract the aqueous layer with ethyl acetate
  4. washwash the organic layer with saturated aqueous sodium chloride solution
  5. dry with materialdry (magnesium sulfate)
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-786c264887874d0a88f77749394f9582
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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