tert-Butyl 4-(acetylthio)piperidine-1-carboxylate → HCID 178502577, compound

HRID 1840512Notes

Reaction equation

HRID 1840512 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([S:14][C:15](=O)[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([SH:14]([CH2:15][CH:16]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[C:6]([O:5][CH3:1])=[O:7])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 1

HCID 22494773tert-Butyl 4-(acetylthio)piperidine-1-carboxylate

Product 1

HCID 178502577HCID 178502577, compoundYield 87.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-10 °C

Procedure

Intermediate 6 (0.50 g) and Intermediate 12 (0.46 g) were combined in anhydrous methanol, degassed, cooled to −10° C., and treated with sodium bis(trimethylsilyl)amide (1.78 ml, as a 1.0 M solution in tetrahydrofuran), and the mixture stirred for 18 h, slowly warming to room temperature. The reaction was then reduced in vacuo, diluted with water (20 ml) and extracted with ethyl acetate (2×20 ml). The combined organic extracts were washed with aqueous 2% citric acid (20 ml), water (20 ml), saturated sodium bicarbonate (20 ml), saturated brine (20 ml), dried (Na2SO4) and solvents removed in vacuo to leave a straw coloured oil. This crude product was the purified by silica gel column chromatography, eluting with a gradient of 2% diethyl ether in dichloromethane rising to 4% diethyl ether in dichloromethane, to furnish the title compound as a colourless oil (0.29 g, 44%).

Workup

  1. customdegassed
  2. additiontreated with sodium bis(trimethylsilyl)amide (1.78 ml
  3. temperatureslowly warming to room temperature
  4. additiondiluted with water (20 ml)
  5. extractionextracted with ethyl acetate (2×20 ml)
  6. washThe combined organic extracts were washed with aqueous 2% citric acid (20 ml), water (20 ml), saturated sodium bicarbonate (20 ml), saturated brine (20 ml)
  7. dry with materialdried (Na2SO4) and solvents
  8. customremoved in vacuo
  9. customto leave a straw coloured oil
  10. custompurified by silica gel column chromatography
  11. washeluting with a gradient of 2% diethyl ether in dichloromethane rising to 4% diethyl ether in dichloromethane

Sources & evidence

ORD record
ord-cc8df1d01fdf4b24be5efd434c6631fa
Source dataset
uspto-grants-2004_01
Patent number
US06680338B2

Reaction notes

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