Methyl 4-Formylbenzoate → Methyl 4-[(R)-1-[(2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl]-1-(3-tert-butyldimethylsilyloxyphenyl)methyl]benzoate

HRID 1057396Notes

Reaction equation

HRID 1057396 reaction equation
[CH2:1]([N:4]1[CH2:9][C@H:8]([CH3:10])[NH:7][CH2:6][C@H:5]1[CH3:11])[CH:2]=[CH2:3].N1C2C=CC=CC=2N=N1.[CH:21]([C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=1)=O.[Si:33]([O:40][C:41]1[CH:42]=[C:43]([Mg]Br)[CH:44]=[CH:45][CH:46]=1)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>C1(C)C=CC=CC=1.O1CCCC1.O>[CH2:1]([N:4]1[C@H:5]([CH3:11])[CH2:6][N:7]([C@H:21]([C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=2)[C:43]2[CH:44]=[CH:45][CH:46]=[C:41]([O:40][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:34])[CH3:35])[CH:42]=2)[C@@H:8]([CH3:10])[CH2:9]1)[CH:2]=[CH2:3]

Participants

8

Reactant 4

HCID 15294Methyl 4-FormylbenzoateHCID 10534891(-)-(2R,5S)-1-allyl-2,5-dimethylpiperazineHCID 178418385HCID 178418385, compoundHCID 178455064HCID 178455064, compound

Product 1

HCID 59037998Methyl 4-[(R)-1-[(2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl]-1-(3-tert-butyldimethylsilyloxyphenyl)methyl]benzoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-17.5 °C

Procedure

A solution of (−)-(2R,5S)-1-allyl-2,5-dimethylpiperazine (22.26 g), benzotriazole (17.18 g) and methyl 4-formylbenzoate (23.7 g) in toluene (400 ml) was heated under reflux with azeotropic removal of water for 3 hours. The solution was cooled and added to a cold solution (−20° C.) of 3-tert-butyldimethylsilyloxyphenylmagnesium bromide (prepared from 82.9 g of corresponding bromide and 7.29 g of magnesium turnings) in tetrahydrofuran (300 ml) at such a rate as to maintain the internal temperature in the range −20 to −15° C. The resulting solution was stirred at −20° C. for 1.5 hours and then warmed to room temperature, quenched with saturated aqueous ammonium chloride solution (200 ml). The layers were separated and the aqueous solution extracted with ethyl acetate (2×200 ml). The combined organic extracts were dried (MgSO4) and evaporated to dryness in vacuo. The residue was purified by column chromatography over silica gel (85/15/2 hexane/ethyl acetate/diethyl amine) to afford the title compound, 54.45 g.

Workup

  1. temperatureThe solution was cooled
  2. temperaturewarmed to room temperature
  3. customquenched with saturated aqueous ammonium chloride solution (200 ml)
  4. customThe layers were separated
  5. extractionthe aqueous solution extracted with ethyl acetate (2×200 ml)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. customevaporated to dryness in vacuo
  8. customThe residue was purified by column chromatography over silica gel (85/15/2 hexane/ethyl acetate/diethyl amine)

Sources & evidence

ORD record
ord-ebd0c3692d3646278f632ab9c539bd39
Source dataset
uspto-grants-2003_02
Patent number
US06514975B1

Reaction notes

Loading…