Tetrahydrofuran → HCID 57753886, compound

HRID 225834Notes

Reaction equation

HRID 225834 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].[O:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1>>[CH2:21]([O:17][C:9]1[N:8]=[C:13]([O:14][CH:11]2[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]2)[CH:12]=[CH:11][CH:10]=1)[C:20]1[CH:6]=[CH:4][CH:5]=[CH:18][CH:19]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 57753886HCID 57753886, compoundYield 49%

Conditions

Temperature
55 °C

Procedure

A solution of 1-boc-4-hydroxypiperidine (501 mg, 2.49 mmol) in tetrahydrofuran (10 mL) was added dropwise to a suspension of sodium hydride (60% dispersion in mineral oil, 65 mg, 2.74 mmol) and the mixture was heated at 55° C. for 1 hour. The reaction mixture was then cooled to room temperature, a solution of the product of preparation 111 (506 mg, 2.49 mmol) in tetrahydrofuran (3 mL) was added dropwise and the mixture was stirred at room temperature for 45 minutes and at 70° C. for 18 hours. The cooled reaction mixture was partitioned between ethyl acetate (20 mL) and water (10 mL), the organic layer was separated, washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by column chromatography on silica gel, eluting with pentane:ethyl acetate, 100:0 to 90:10, afforded the title compound as a white solid in 49% yield, 470 mg. LRMS APCI m/z 385 [M+H]+

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. additionwas added dropwise
  3. customThe cooled reaction mixture
  4. customwas partitioned between ethyl acetate (20 mL) and water (10 mL)
  5. customthe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by column chromatography on silica gel
  10. washeluting with pentane

Sources & evidence

ORD record
ord-09411ecee7fc4a0b87747ef6b19466e1
Source dataset
uspto-grants-2009_07
Patent number
US07557131B2

Reaction notes

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