Water → HCID 69316455, compound

HRID 2410367Notes

Reaction equation

HRID 2410367 reaction equation
[H-].[Na+].[OH:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][C@H:5]1[O:9][C:10]1[C:15]2[C:16]([O:19][CH2:20][CH:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)=[N:17][O:18][C:14]=2[CH:13]=[CH:12][CH:11]=1.[CH3:34]I.O>O1CCCC1>[CH3:34][O:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][C@H:5]1[O:9][C:10]1[C:15]2[C:16]([O:19][CH2:20][CH:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)=[N:17][O:18][C:14]=2[CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69317858HCID 69317858, compound

Product 1

HCID 69316455HCID 69316455, compoundYield 94.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (60% oil dispersion 11 mg, 0.277 mmol) in tetrahydrofuran (5.0 mL) was added a solution of tert-butyl 4-{[(4-{[trans-2-hydroxycyclopentyl]oxy}-1,2-benzisoxazol-3-yl)oxy]methyl}piperidine-1-carboxylate (80 mg, 0.185 mmol, EXAMPLE 32, Step 1) in tetrahydrofuran (2.0 mL) at 0° C. under nitrogen. After being stirred at 0° C. for 30 min, methyliodide (14 μL, 0.222 mmol) was added to the mixture. The mixture was stirred at 0° C. for 3 h, water was added to the mixture. The mixture was extracted with ethyl acetate (30 mL×2) and washed with brine. The extracts were combined and dried over sodium sulfate and concentrated in vacuo to give an oil. The residual oil was purified by silica gel column chromatography (hexane/ethyl acetate 5:1 to 4:1) to give 78 mg (94%) of the title compound as a colorless viscous oil.

Workup

  1. stirringThe mixture was stirred at 0° C. for 3 h
  2. extractionThe mixture was extracted with ethyl acetate (30 mL×2)
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give an oil
  7. customThe residual oil was purified by silica gel column chromatography (hexane/ethyl acetate 5:1 to 4:1)

Sources & evidence

ORD record
ord-f0fe10db2afc4e6b913ddfbd7e9c8fa0
Source dataset
uspto-grants-2014_08
Patent number
US08816090B2

Reaction notes

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