Lithium Hexamethyldisilazide → (R)-4-benzyl-3-((R)-2-(4-methoxy-3-(3-methoxypropoxy)benzyl)-3-methylbutanoyl)oxazolidin-2-one

HRID 2258288Notes

Reaction equation

HRID 2258288 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][CH:16]([CH3:18])[CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:30][O:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Br)=[CH:34][C:33]=1[O:40][CH2:41][CH2:42][CH2:43][O:44][CH3:45]>O1CCCC1>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@H:15]([CH2:36][C:35]1[CH:38]=[CH:39][C:32]([O:31][CH3:30])=[C:33]([O:40][CH2:41][CH2:42][CH2:43][O:44][CH3:45])[CH:34]=1)[CH:16]([CH3:17])[CH3:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 11391340(4R)-4-Benzyl-3-(3-methylbutanoyl)-1,3-oxazolidin-2-oneHCID 115583294-(Bromomethyl)-1-methoxy-2-(3-methoxypropoxy)benzene

Product 1

HCID 22865790(R)-4-benzyl-3-((R)-2-(4-methoxy-3-(3-methoxypropoxy)benzyl)-3-methylbutanoyl)oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-70 °C

Procedure

Under an inert atmosphere at -70° C. a solution of 4(R)-benzyl-3-isovaleroyl-oxazolidin-2-one (156.6 g) in tetrahydrofuran (500 ml) is added to a 1M lithium hexamethyldisilazide solution in tetrahydrofuran (600 ml, 0.60 mol) which has been diluted with anhydrous tetrahydrofuran (600 ml), and the batch is stirred for a further 75 minutes at -70° C. A solution of 4-methoxy-3-(3-methoxypropoxy)-benzyl bromide (145 g) in tetrahydrofuran (500 ml) is then added. The reaction temperature is allowed to rise from -70° C. to 0° C. over a period of 2 hours and the mixture is stirred at 0° C. for a further 18 hours. The reaction is quenched by the addition of a 10% aqueous ammonium chloride solution (250 ml) and the mixture is concentrated under reduced pressure and the aqueous phase is extracted with ethyl acetate (3×1.2 liters). The organic phases are washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated. Purification of the residue by FC on silica gel (hexane/ethyl acetate 1:1) yields the title compound in the form of a white solid (202 g): m.p. 55°-56° C. (recrystallised from diethyl ether/hexane). Rf (ethyl acetate/hexane 1:2)=0.30. Anal. C27H35NO6 (469.58): calc. C, 69.06; H, 7.51; N, 2.98; found C, 68.64; H, 7.49; N, 3.12.

Workup

  1. waitto rise from -70° C. to 0° C. over a period of 2 hours
  2. stirringthe mixture is stirred at 0° C. for a further 18 hours
  3. customThe reaction is quenched by the addition of a 10% aqueous ammonium chloride solution (250 ml)
  4. concentrationthe mixture is concentrated under reduced pressure
  5. extractionthe aqueous phase is extracted with ethyl acetate (3×1.2 liters)
  6. washThe organic phases are washed with saturated sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customPurification of the residue by FC on silica gel (hexane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-e73c671db6a04abf96de586ad7c97516
Source dataset
uspto-grants-1997_08
Patent number
US05659065

Reaction notes

Loading…