N-Boc-pyrrolidine → (R)-tert-butyl 2-((1S,2S)-2-(dibenzylamino)-1-hydroxy-3-phenylpropyl)pyrrolidine-1-carboxylate

HRID 732347Notes

Reaction equation

HRID 732347 reaction equation
C([Li])(CC)C.C1C[C@H]2N(C[C@H]3[C@@H]4CCCCN4C[C@@H]2C3)CC1.[C:23]([N:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1)([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].[CH2:35]([N:42]([CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[C@@H:43]([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[CH:44]=[O:45])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>C(OCC)C.C(O)(=O)C>[C:26]([O:25][C:23]([N:30]1[CH2:31][CH2:32][CH2:33][C@@H:34]1[C@@H:44]([OH:45])[C@@H:43]([N:42]([CH2:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)[CH2:53][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)[CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:24])([CH3:29])([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 643455N-Boc-pyrrolidineHCID 644020SparteineHCID 9883943(alphaS)-alpha-[Bis(phenylmethyl)amino]benzenepropanalHCID 178418400CID 53628100

Product 1

HCID 58699983(R)-tert-butyl 2-((1S,2S)-2-(dibenzylamino)-1-hydroxy-3-phenylpropyl)pyrrolidine-1-carboxylateYield 60.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolvent3×

Procedure

Add sec-butyllithium (1.29 mL, 1.8 mmol) dropwise to a solution of (−)-sparteine (0.44 mL, 1.36 mmol) in diethyl ether (10 mL) over 3 min at −78° C. Add N-Boc-pyrrolidine (0.245 mL, 1.4 mmol) in diethyl ether (2 mL) dropwise over 10 min. Stir 2 h, add 2-(S)-dibenzylamino-3-phenylpropionaldehyde (0.69 g, 2.1 mmol) in diethyl ether (1.8 mL) over 5 min and stir 20 min. Add acetic acid (0.16 mL) and warn to room temperature. Add saturated aqueous sodium chloride (20 mL), separate layers, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a foam (0.421 g, 60%).

Workup

  1. stirringstir 20 min
  2. customwarn to room temperature
  3. customAdd saturated aqueous sodium chloride (20 mL), separate layers
  4. dry with materialdry (magnesium sulfate)
  5. concentrationconcentrate
  6. custompurify
  7. wash(silica gel chromatography, eluting with hexanes and ethyl acetate)

Sources & evidence

ORD record
ord-96e470cbeb4340c79c3cdff538b20c9a
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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