Ethanol → tert-Butyl {(3S)-3-methyl-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamate

HRID 17631Notes

Reaction equation

HRID 17631 reaction equation
[CH3:1][C@:2]1([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:6][C:5](=O)[N:4]([C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:9])[CH2:3]1.B.O1CCCC1.C(O)C.C(N(CC)CC)C>O1CCCC1.O>[CH3:1][C@:2]1([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:6][CH2:5][N:4]([C@@H:8]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH3:9])[CH2:3]1

Participants

7

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 2723981Borane;tetrahydrofuranHCID 51041667tert-Butyl {(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamate

Product 1

HCID 51041668tert-Butyl {(3S)-3-methyl-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamateYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl {(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamate (I-343) (500 mg, 1.57 mmol) was dissolved in tetrahydrofuran (15 ml), and with cooling with ice, borane/tetrahydrofuran complex (1.2 mol/l tetrahydrofuran solution) (3.93 ml, 4.71 mmol) was added, followed by stirring at room temperature for 17 hours. Ethanol (12 ml), triethylamine (4 ml) and water (4 ml) were added to the reaction liquid, followed by stirring in an oil bath at 90° C. for 3 hours. The reaction liquid was concentrated under reduced pressure, dissolved in ethyl acetate, and washed with an aqueous saturated sodium hydrogencarbonate solution and saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, and the residue obtained by concentration was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:1→1:2, v/v) to obtain the entitled compound (406 mg, 85%) as a colorless oily substance.

Workup

  1. additionwas added
  2. stirringby stirring in an oil bath at 90° C. for 3 hours
  3. customThe reaction liquid
  4. concentrationwas concentrated under reduced pressure
  5. dissolutiondissolved in ethyl acetate
  6. washwashed with an aqueous saturated sodium hydrogencarbonate solution and saturated brine
  7. dry with materialAfter drying over anhydrous sodium sulfate
  8. customthe insoluble matter was separated by filtration
  9. customthe residue obtained by concentration
  10. customwas purified by silica gel column chromatography (eluent, n-hexane

Sources & evidence

ORD record
ord-813c5ef30a1b4957b421e1be8e5d6739
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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