Sodium hydride → [2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine

HRID 355376Notes

Reaction equation

HRID 355376 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([OH:16])[C@@H:11]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].CS(O[CH2:28][C:29]1[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[C:31]([N:39]2[C:43]([CH3:44])=[N:42][N:41]=[N:40]2)[CH:30]=1)(=O)=O.C(=O)([O-])O.[Na+]>CN(C)C=O.O>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([O:16][CH2:28][C:29]2[CH:34]=[C:33]([C:35]([F:36])([F:37])[F:38])[CH:32]=[C:31]([N:39]3[C:43]([CH3:44])=[N:42][N:41]=[N:40]3)[CH:30]=2)[C@@H:11]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 10901890(2S,3S)-1-t-Butyloxycarbonyl-3-hydroxy-2-phenylpiperidineHCID 189421531-(Methanesulfonyloxymethyl)-3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)benzene

Product 1

HCID 57127052[2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)phenylmethoxy]piperidineYield 51.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil, 24 mg, 0.6 mmol) was added to a stirred, cooled (0° C.) solution of [2S,3S]-1-tert-butoxycarbonyl-2-phenylpiperidin-3-ol (138 mg, 0.5 mmol) in N,N-dimethylformamide (2 ml). The mixture was stirred at room temperature for 30 minutes, cooled in ice and 1-(methanesulfonyloxymethyl)-3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)benzene (168 mg, 0.5 mmol) in N,N-dimethylformamide (2 ml) was added. The mixture was stirred at room temperature for 66 hours, saturated aqueous sodium hydrogen carbonate (20 ml) and water (10 ml) were added and the mixture was extracted with ethyl acetate (3×20 ml). The combined organic fractions were washed with saturated aqueous sodium hydrogen carbonate (4×20 ml) and brine (20 ml), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by MPLC on silica gel, eluting with ethyl acetate/hexane (40:60 increasing to 60:40) to give [2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine as a pale yellow oil (133 mg, 51%), 1H (CDCl3) δ 7.69 (1H, s), 7.65 (1H, s), 7.52 (3H, m), 7.31-7.19 (3H, m), 5.68 (1H, br s), 4.77 (2H, s), 3.92 (2H, m), 2.78 (1H, m), 2.58 (3H, s), 2.00 (2H, m), 1.66 (2H, m), and 1.45 (9H, s). m/z 518 (M+H+).

Workup

  1. temperaturecooled in ice
  2. stirringThe mixture was stirred at room temperature for 66 hours
  3. extractionthe mixture was extracted with ethyl acetate (3×20 ml)
  4. washThe combined organic fractions were washed with saturated aqueous sodium hydrogen carbonate (4×20 ml) and brine (20 ml)
  5. dry with materialdried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by MPLC on silica gel
  8. washeluting with ethyl acetate/hexane (40:60 increasing to 60:40)

Sources & evidence

ORD record
ord-671722c8f5a64181995815924ca41e62
Source dataset
uspto-grants-1998_11
Patent number
US05830892

Reaction notes

Loading…