Sodium borohydride → 1-Benzyloxycarbonyl-2-(1-hydroxyethyl)-4-tert-butyloxycarbonyl-piperazine

HRID 429285Notes

Reaction equation

HRID 429285 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]1[C:24](=[O:26])[CH3:25])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>C1COCC1.CCO>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:13][CH:12]1[CH:24]([OH:26])[CH3:25])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 18342886HCID 18342886, compound

Product 1

HCID 183428851-Benzyloxycarbonyl-2-(1-hydroxyethyl)-4-tert-butyloxycarbonyl-piperazine

Reagents, catalysts & solvents 1

HCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

To a solution of 6.50 g of 1-benzyloxycarbonyl-2-acetyl-4-tert-butyloxycarbonyl-piperazine in 150 mL of 1:1 THF-EtOH was added 1.35 g of sodium borohydride, in several portions. The mixture was stirred at room temperature for 30 min, then quenched by slow addition of 100 mL of saturated NaHCO3. The mixture was diluted with 150 mL of water and the phases were separated. The aqueous phase was extracted with 2×100 mL of EtOAc. The combined organics were washed with 100 mL of brine, dried over MgSO4, and concentrated. The residue was purified by flash chromatography, eluting with 2:1 hexanes-EtOAc, to yield 3.05 g of diastereomer 1 and 272 g of diastereomer 2. Data for diastereomer 1. Rf 0.63 (1:1 hexanes-EtOAc). 1H NMR (500 MHz, DMSO-d6, 75° C.): δ7.24-7.40 (m, 5H), 5.10 (s, 2H), 4.52 (d, J=5.0 Hz, 1H), 4.20 (d, J=13.1 Hz, 1H), 3.71-3.92 (m, 4H), 2.76-2.96 (m, 3H),1.40 (s, 9H), 1.00 (d, J=5.5 Hz, 3H). Mass spectrum (ESI) 309.1 (M-BOC). Data for diastereomer 2. Rf 0.53 (1:1 hexanes-EtOAc). 1H NMR (500 MHz, DMSO-d6, 75° C.): δ7.23-7.40 (m, 5H), 5.08 (s, 2H), 4.41 (br s, 1H), 3.74-3.92 (m, 5H), 3.02-3.11 (m, 1H),2.98 (dd, J=3.4, 13.5 Hz, 1H), 2.28 (br t, J=11.7 Hz, 1H), 1.40 (s, 9H), 1.16 (d, J=6.0 Hz, 3H).

Workup

  1. customquenched by slow addition of 100 mL of saturated NaHCO3
  2. additionThe mixture was diluted with 150 mL of water
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted with 2×100 mL of EtOAc
  5. washThe combined organics were washed with 100 mL of brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography
  9. washeluting with 2:1 hexanes-EtOAc
  10. customto yield 3.05 g of diastereomer 1 and 272 g of diastereomer 2

Sources & evidence

ORD record
ord-abf6ee6b8b264baea53155f41f81ff50
Source dataset
uspto-grants-2001_11
Patent number
US06316444B1

Reaction notes

Loading…