Trimethylsilylacetylene → 1-Boc-3-ethynyl-3-hydroxypiperidine

HRID 2216360Notes

Reaction equation

HRID 2216360 reaction equation
C([Li])CCC.C[Si]([C:10]#[CH:11])(C)C.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH2:22][C:21](=[O:25])[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].[Cl-].N>O1CCCC1.CCCCCC>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH2:22][C:21]([C:10]#[CH:11])([OH:25])[CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 4

HCID 66111TrimethylsilylacetyleneHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 20976574Ammonia chlorideHCID 178418339Butyllithium

Product 1

HCID 219422481-Boc-3-ethynyl-3-hydroxypiperidineYield 71.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

In a dry ice-acetone bath, 40 ml of a 1.6 M hexane solution of n-butyllithium was added dropwise to a solution of 6.07 g of trimethylsilylacetylene in 100 ml of tetrahydrofuran. After the temperature was once elevated to 0° C., the mixture was cooled again in a dry ice-acetone bath and a solution of 5.97 g of 1-tert-butoxycarbonylpiperidin-3-one in 50 ml of tetrahydrofuran was added dropwise thereto. After 1 hour, aqueous ammonia chloride was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and then evaporated. The residue was purified by silica gel column chromatography with 30% ethyl acetate/hexane. To the resulting compound were added 10 g of anhydrous potassium carbonate and 100 ml of methanol, followed by stirring for 2 hours. Water was added thereto, and the mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate and evaporated, to give 4.8 g of the title compound.

Workup

  1. customwas once elevated to 0° C.
  2. temperaturethe mixture was cooled again in a dry ice-acetone bath
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated
  7. customThe residue was purified by silica gel column chromatography with 30% ethyl acetate/hexane
  8. additionTo the resulting compound were added 10 g of anhydrous potassium carbonate and 100 ml of methanol
  9. additionWater was added
  10. extractionthe mixture was extracted with ethyl acetate
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customevaporated

Sources & evidence

ORD record
ord-8603fd45a8fd4289a6acbbf889dd6bf3
Source dataset
uspto-grants-2006_09
Patent number
US07112593B2

Reaction notes

Loading…