Methanesulfonyl chloride → 4-(1-(3-(Tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)butyl methanesulfonate

HRID 1855049Notes

Reaction equation

HRID 1855049 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[O:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[O:12][C:13]1[CH:14]=[C:15]([C:19]23[CH2:26][CH2:25][C:22]([CH2:27][CH2:28][CH2:29][CH2:30][OH:31])([CH2:23][CH2:24]2)[CH2:21][O:20]3)[CH:16]=[CH:17][CH:18]=1>C(Cl)Cl>[CH3:1][S:2]([O:31][CH2:30][CH2:29][CH2:28][CH2:27][C:22]12[CH2:23][CH2:24][C:19]([C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([O:12][CH:7]4[CH2:8][CH2:9][CH2:10][CH2:11][O:6]4)[CH:14]=3)([CH2:26][CH2:25]1)[O:20][CH2:21]2)(=[O:4])=[O:3]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 904083944-(1-(3-(Tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)butan-1-ol

Product 1

HCID 904083254-(1-(3-(Tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)butyl methanesulfonateYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

MsCl (0.036 ml, 0.462 mmol) was added to a solution of 4-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2] octan-4-yl)butan-1-ol (111 mg, 0.31 mmol) and TEA (0.129 ml, 0.92 mmol) in DCM (2 mL) at 0° C. The reaction was then stirred at rt for 2 h and concentrated in vacuo. The residue was dissolved in EtOAc (5 mL), washed with water (4×5 mL), dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on SiO2 (gradient from 0 to 50% EtOAc: hexanes) to afford the title compound (133 mg, 98% yield) as a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.23 (t, J=8.0 Hz, 1H), 7.13-7.10 (m, 1H), 7.03-6.99 (m, 1H), 6.94 (ddd, J=8.2, 2.5, 0.8 Hz, 1H), 5.44 (t, J=3.2 Hz, 1H), 4.25 (t, J=6.5 Hz, 2H), 4.04-3.88 (m, 1H), 3.82 (s, 2H), 3.67-3.55 (m, 1H), 3.03 (s, 3H), 2.06-1.99 (m, 5H), 1.90-1.83 (m, 2H), 1.79-1.57 (m, 9H), 1.43-1.34 (m, 2H), 1.23-1.16 (m, 2H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc (5 mL)
  3. washwashed with water (4×5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on SiO2 (gradient from 0 to 50% EtOAc: hexanes)

Sources & evidence

ORD record
ord-64fc3346bcee49d3885658ae863c4122
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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