Acetic Acid → (R)-tert-butyl 4-(3-hydroxy-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407873Notes

Reaction equation

HRID 407873 reaction equation
CC1(C)[O:6][C@H:5]([CH2:7][CH:8]=O)[C:4](=[O:10])O1.[NH2:12][CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)CCl>[OH:6][C@@H:5]1[CH2:7][CH2:8][N:12]([CH:13]2[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18]2)[C:4]1=[O:10]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 12682914-Amino-1-Boc-piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 24864236HCID 24864236, compound

Product 1

HCID 86688071(R)-tert-butyl 4-(3-hydroxy-2-oxopyrrolidin-1-yl)piperidine-1-carboxylateYield 71.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

(R)-2-(2,2-Dimethyl-5-oxo-1,3-dioxolan-4-yl)acetaldehyde (16 g, 101 mmol) was dissolved in ClCH2CH2Cl (500 mL) and tert-butyl 4-aminopiperidine-1-carboxylate (40.5 g, 202 mmol) and acetic acid (6.94 mL, 121 mmol) were added and stirred at ambient temperature for 15 minutes. NaBH(OAc)3 (64.3 g, 304 mmol) was added in 3 portions and the reaction stirred at ambient temperature overnight. The reaction was carefully quenched with saturated aqueous NaHCO3. The reaction was partitioned between aqueous NaHCO3 and CH2Cl2, extracted, washed with 10% citric acid, brine, dried over Na2SO4, filtered and concentrated. The solids were purified over silica gel (5 to 10% methanol in EtOAc) to afford (R)-tert-butyl 4-(3-hydroxy-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (20.5 g, 72.1 mmol, 71.3% yield) as a white solid.

Workup

  1. stirringthe reaction stirred at ambient temperature overnight
  2. customThe reaction was carefully quenched with saturated aqueous NaHCO3
  3. customThe reaction was partitioned between aqueous NaHCO3 and CH2Cl2
  4. extractionextracted
  5. washwashed with 10% citric acid, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe solids were purified over silica gel (5 to 10% methanol in EtOAc)

Sources & evidence

ORD record
ord-cf8b31fc680049fea0e5df94743eab5e
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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