Tetrahydrofuran → HCID 12638305, compound

HRID 1759606Notes

Reaction equation

HRID 1759606 reaction equation
[O:1]=[C:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:3]1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:18][CH:17]=1.C1COCC1.[H-].[Na+].Br[CH2:38][C:39]([O:41][CH3:42])=[O:40]>O>[C:11]([O:10][C:8]([N:4]1[CH2:5][CH2:6][N:7]([CH2:38][C:39]([O:41][CH3:42])=[O:40])[C:2](=[O:1])[CH:3]1[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:20][CH:21]=1)=[O:9])([CH3:13])([CH3:14])[CH3:12]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 12638302HCID 12638302, compound

Product 1

HCID 12638305HCID 12638305, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of t-boc-(4-benzyloxybenzyl)piperazinone 3a (2.66 g, 6.72×10-3 mole) and dry THF (20 ml) under argon at room temperature is added portionwise NaH (0.30 g, 7.4×10-3 mole, 59% oil dispersion). After stirring 1/2 hour at room temperature a solution of methyl α-bromoacetate (0.62 ml, 7.4×10-3 mole) is added via syringe. After stirring overnight the reaction mixture is poured into water which is subsequently extracted with Et2O (3 times). The combined ethereal extracts are washed with saturated aqueous NaCl before being dried over Na2SO4. Filtration of the drying agent and evaporation of the filtrate affords a viscous oil which after column chromatography (silica gel, 10% EtOAc/CHCl3) gives a clear, colorless oil. After standing in the refrigerator this oil crystallizes. The resulting solid is triturated with hexane and collected by filtration affording 4a as colorless matted needles: 2.3 g (74%), m.p. 84°-87° C.

Workup

  1. additionis added via syringe
  2. extractionis subsequently extracted with Et2O (3 times)
  3. washThe combined ethereal extracts are washed with saturated aqueous NaCl
  4. dry with materialbefore being dried over Na2SO4
  5. filtrationFiltration of the drying agent and evaporation of the filtrate
  6. customaffords a viscous oil which after column chromatography (silica gel, 10% EtOAc/CHCl3)
  7. customgives a clear, colorless oil
  8. customcrystallizes
  9. customThe resulting solid is triturated with hexane
  10. filtrationcollected by filtration

Sources & evidence

ORD record
ord-cae30176cc684d4ba793e8be9855e09b
Source dataset
uspto-grants-1982_07
Patent number
US04341698

Reaction notes

Loading…