Sodium Hydroxide → (1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethanol

HRID 423636Notes

Reaction equation

HRID 423636 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]=[C:7](C(Cl)(Cl)Cl)[O:6][N:5]=1)[CH3:3].[NH:13]1[CH2:18][CH2:17][CH:16]([C@H:19]([OH:21])[CH3:20])[CH2:15][CH2:14]1.[OH-].[Na+]>CO>[CH3:1][CH:2]([C:4]1[N:8]=[C:7]([N:13]2[CH2:18][CH2:17][CH:16]([C@H:19]([OH:21])[CH3:20])[CH2:15][CH2:14]2)[O:6][N:5]=1)[CH3:3]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 40614391(R)-1-(Piperidin-4-YL)ethanolHCID 509865513-(Propan-2-yl)-5-(trichloromethyl)-1,2,4-oxadiazole

Product 1

HCID 66673480(1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethanolYield 68%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of 3-(1-methylethyl)-5-(trichloromethyl)-1,2,4-oxadiazole (25.8 g, 112 mmol) and (1R)-1-(4-piperidinyl)ethanol (13.4 g, 104 mmol) in MeOH (15 mL) was stirred at ambient temperature under a stream of nitrogen for 7 days. The reaction was diluted with MeOH (40 mL), cooled in an ice bath and 1N NaOH (25 mL) was added. The mixture was allowed to warm to ambient temperature and stir for 1 h. The reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL) and the layers were separated. The aqueous layer was saturated with NaCl and extracted with EtOAc (200 mL). The combined EtOAc layers were dried over MgSO4, concentrated and placed under high vacuum for 18 h to afford (1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethanol (16.75 g, 68%) as an orange oil. 1H NMR (400 MHz, CDCl3): δ 4.14 (m, 2H), 3.57 (quint, 1H, J=6.3 Hz), 2.98 (m, 2H), 2.83 (septet, 1H, J=7.0 Hz), 1.90 (m, 1H), 1.86 (br, 1H), 1.67 (m, 1H), 1.45 (m, 1H), 1.33 (m, 2H), 1.23 (d, 6H, J=7.0 Hz), 1.16 (d, 3H, J=6.3 Hz); LRMS (ESI), m/z 240 (M+H).

Workup

  1. temperaturecooled in an ice bath
  2. customThe reaction was partitioned in EtOAc (300 mL)/1N NaOH (75 mL)
  3. customthe layers were separated
  4. extractionextracted with EtOAc (200 mL)
  5. dry with materialThe combined EtOAc layers were dried over MgSO4
  6. concentrationconcentrated
  7. waitplaced under high vacuum for 18 h

Sources & evidence

ORD record
ord-b8814349b14e4749816e529ae1319b1c
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

Loading…