Dimethyl Sulfoxide → 1-(4-Benzyl-4-hydroxy-piperidin-1-yl)-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propan-2-one

HRID 1419928Notes

Reaction equation

HRID 1419928 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([C:18]1([OH:42])[CH2:23][CH2:22][N:21]([CH2:24][CH:25]([OH:41])[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])=[CH:29][CH:28]=2)[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.[NH4+].[Cl-]>C(Cl)Cl>[CH2:11]([C:18]1([OH:42])[CH2:19][CH2:20][N:21]([CH2:24][C:25](=[O:41])[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][Si:34]([C:37]([CH3:38])([CH3:39])[CH3:40])([CH3:35])[CH3:36])=[CH:29][CH:28]=2)[CH2:22][CH2:23]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 70045791(RS)-4-Benzyl-1-{3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-hydroxy-propyl}-piperidin-4-ol

Product 1

HCID 700483361-(4-Benzyl-4-hydroxy-piperidin-1-yl)-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propan-2-oneYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of oxalylchloride (0.28 ml, 3.3 mmol) in CH2Cl2 (4 ml) at -78° C. was added dropwise dimethyl sulfoxide (DMSO) (0.47 ml, 6.6 mmol). After 30 min., a solution of (RS)-4-Benzyl-1-{3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-hydroxy-propyl}-piperidin-4-ol (0.75 g, 1.65 mmol) in CH2Cl2 (4 ml) was added. After another hour at -78° C., triethylamine (1.8 ml, 13.2 mmol) was added and reaction mixture was allowed to warm up slowly to room temperature. After 1 hour, 20% NH4Cl (15 ml) was added, the resulting aqueous phase was extracted with CH2Cl2 (3×30 ml). Combined organic phases were dried over Na2SO4 and concentrated. The residue was chromatographed over silica gel (hexane-ethylacetate 1:1 then ethyl acetate) to provide 1-(4-Benzyl-4-hydroxy-piperidin-1-yl)-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propan-2-one (0.4 g, 54%) as a yellow oil, and MS: m/e=454.5 (M+H+).

Workup

  1. waitAfter another hour at -78° C.
  2. customreaction mixture
  3. waitAfter 1 hour
  4. extractionthe resulting aqueous phase was extracted with CH2Cl2 (3×30 ml)
  5. dry with materialCombined organic phases were dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was chromatographed over silica gel (hexane-ethylacetate 1:1

Sources & evidence

ORD record
ord-bf8e4060854c4a81bd229698660ca7dc
Source dataset
uspto-grants-1999_03
Patent number
US05889026

Reaction notes

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