Triethylamine → (1-(3-Isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methyl methanesulfonate

HRID 423544

Reaction equation

HRID 423544 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][OH:16])[CH2:11][CH2:10]2)[O:6][N:5]=1)[CH3:3].C(N(CC)CC)C.[CH3:24][S:25](Cl)(=[O:27])=[O:26]>ClCCl>[CH3:24][S:25]([O:16][CH2:15][CH:12]1[CH2:13][CH2:14][N:9]([C:7]2[O:6][N:5]=[C:4]([CH:2]([CH3:1])[CH3:3])[N:8]=2)[CH2:10][CH2:11]1)(=[O:27])=[O:26]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 57930076{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methanol

Product 1

HCID 57930198(1-(3-Isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methyl methanesulfonateYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

A solution of {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methanol (prepared as in Step 3, 174 g, 0.77 mol) and triethylamine (140 mL, 1.0 mol) in dichloromethane (1 L) at 5° C. was treated with a solution of methanesulfonyl chloride (69 mL, 0.89 mol) in dichloromethane (150 mL) over a 1 h period. The mixture was stirred at 5° C. for 30 min, and then was quenched by the addition of water (400 mL). The mixture was stirred for 30 min, and then the organic extract was washed with water (2×400 mL), dried (MgSO4) and concentrated. The residue was treated with heptane (1 L), stirred for 3 h, and the resulting solid was collected by filtration (heptane wash) and air-dried to afford {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl methanesulfonate (219.7 g, 94%) as an off-white solid. 1NMR (400 MHz, CDCl3): δ 4.21-4.15 (m, 2H), 4.08 (d, 2H, J=6.6 Hz), 3.04 (m, 2H), 3.01 (s, 3H), 2.86 (septet, 1H, J=6.9 Hz), 2.05-1.93 (m, 1H), 1.88-1.81 (m, 2H), 1.43-1.31 (m, 2H), 1.26 (d, 6H, J=6.8 Hz); LRMS (ESI), m/z 304 (M+H).

Workup

  1. customwas quenched by the addition of water (400 mL)
  2. stirringThe mixture was stirred for 30 min
  3. extractionthe organic extract
  4. washwas washed with water (2×400 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. additionThe residue was treated with heptane (1 L)
  8. stirringstirred for 3 h
  9. filtrationthe resulting solid was collected by filtration (heptane wash)
  10. customair-dried

Sources & evidence

ORD record
ord-da90f25b932a427788a740fef9d7b98a
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Linked notes

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