Boron trifluoride → 3-(3,4-Dichlorophenyl)-1-[(3,5-dimethylphenyl)methoxy]-5-(4-hydroxy-4-phenyl-1-piperidinyl)-2-pentanone

HRID 1939842Notes

Reaction equation

HRID 1939842 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:10])[CH:9]=1)[CH2:5][OH:6].B(F)(F)F.[N+](=[CH:17][C:18](=[O:43])[CH:19]([C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[C:37]([Cl:42])[CH:36]=1)[CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][C:25]([OH:34])([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:24][CH2:23]1)=[N-].CCN(CC)CC>C(Cl)Cl>[Cl:42][C:37]1[CH:36]=[C:35]([CH:19]([CH2:20][CH2:21][N:22]2[CH2:23][CH2:24][C:25]([OH:34])([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:26][CH2:27]2)[C:18](=[O:43])[CH2:17][O:6][CH2:5][C:4]2[CH:7]=[C:8]([CH3:10])[CH:9]=[C:2]([CH3:1])[CH:3]=2)[CH:40]=[CH:39][C:38]=1[Cl:41]

Participants

6

Reactant 4

HCID 6356Boron trifluorideHCID 8471TriethylamineHCID 337063,5-Dimethylbenzyl alcoholHCID 539157251-Diazo-3-(3,4-dichlorophenyl)-5-(4-hydroxy-4-phenyl-1-piperidinyl)-2-pentanone

Product 1

HCID 189366073-(3,4-Dichlorophenyl)-1-[(3,5-dimethylphenyl)methoxy]-5-(4-hydroxy-4-phenyl-1-piperidinyl)-2-pentanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Dissolve 3,5-dimethyl benzyl alcohol (1.32 g, 9.71 mmoles) in 4.0 ml of dry CH2Cl2 and add BF3 etherate (0.44 ml, 3.56 mmoles). Add a dry CH2Cl2 solution (2.0 ml.) of the product of Step 5 (0.7 g, 1.62 mmoles) dropwise at room temperature, under N2, over a period of 4.5 h. Stir the mixture at room temperature for another 30 min, then quench the reaction with water (6.0 ml) followed, after 10 min of stirring, by Et3N (2.0 ml). Stir for 15 min, then dilute with 90 ml of CH2Cl2. Wash the organic layer with water and dry it over anhydrous Na2SO4. Purify the reaction mixture by flash chromatography (SiO2), eluting the column first with 30% EtOAc/hexanes, then, after elution of the excess of 3,5-dimethyl benzyl alcohol, change the eluent to 40% EtOAc/Hexanes. Yield: 0.435 g. HRMS (FAB, M+H+): m/e calc'd for [C31H36NO3Cl2 ]+ : 540.2072; found 540.2075.

Workup

  1. customquench
  2. customthe reaction with water (6.0 ml)
  3. waitfollowed, after 10 min
  4. stirringStir for 15 min
  5. washWash the organic layer with water
  6. dry with materialdry it over anhydrous Na2SO4
  7. customPurify the reaction mixture by flash chromatography (SiO2)
  8. washeluting the column first with 30% EtOAc/hexanes
  9. washafter elution of the excess of 3,5-dimethyl benzyl alcohol

Sources & evidence

ORD record
ord-debc306965524740ab03b759040cbb2a
Source dataset
uspto-grants-1997_12
Patent number
US05696267

Reaction notes

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