Propyl mercaptan → N-(2-Propenyl)-cis-2-[4-(1,1-dimethylheptyl)-2-hydroxyphenyl]-4-piperidinol

HRID 371160Notes

Reaction equation

HRID 371160 reaction equation
C(S)CC.C([Li])CCC.[CH2:10]([N:13]1[CH2:18][CH2:17][C@H:16]([OH:19])[CH2:15][C@@H:14]1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:34])([CH3:33])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:22][C:21]=1[O:35]CC1C=CC=CC=1)[CH:11]=[CH2:12].C([S-])CC.[Li+]>O1CCCC1.CCCCCC.CN(C)P(N(C)C)(N(C)C)=O>[CH2:10]([N:13]1[CH2:18][CH2:17][C@H:16]([OH:19])[CH2:15][C@@H:14]1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:34])([CH3:33])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:22][C:21]=1[OH:35])[CH:11]=[CH2:12]

Participants

8

Reactant 4

HCID 7848Propyl mercaptanHCID 10909481Lithium propanethiolateHCID 70490735N-(2-Propenyl)-cis-2-[2-benzyloxy-4-(1,1-dimethylheptyl)phenyl]-4-piperidinolHCID 178418339Butyllithium

Product 1

HCID 70491522N-(2-Propenyl)-cis-2-[4-(1,1-dimethylheptyl)-2-hydroxyphenyl]-4-piperidinolYield 58%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 6.8 ml (74.6 mmole) of propanethiol in 75 ml of tetrahydrofuran is degassed by three freeze-thaw cycles at 0.1 torr. The resultant solution is cooled to -78° C. and 28 ml of 2.5M n-butyllithium in hexane is added. The reaction is then allowed to warm to 25° C. and stirred 3 hours longer. The reaction is evaporated to dryness under high vacuum and the residue dissolved in 70 ml of degassed hexamethylphosphoramide. To a 25° C. degassed solution of 218 mg (0.486 mmole) of N-(2-propenyl)-cis-2-[2-benzyloxy-4-(1,1-dimethylheptyl)phenyl]-4-piperidinol in 1 ml of hexamethylphosphoramide is added 2.2 ml of the above prepared solution of lithium propanethiolate. The reaction is stirred 30 minutes at 25° C. and 1.5 hour at 105° C. followed by cooling to 25° C. The reaction is quenched by addition to 30 ml water and the mixture extracted with 150 ml ethyl ether. The ether extract is washed twice with 30 ml water, once with 30 ml saturated sodium chloride, dried over magnesium sulfate and evaporated to an oil. The crude product is purified via column chromatography on 48 g of silica gel eluting in 8 ml fractions with ethyl ether to give (fractions 12-24) 101 mg (58%) of the title compound as an oil.

Workup

  1. customThe reaction is evaporated to dryness under high vacuum
  2. dissolutionthe residue dissolved in 70 ml of degassed hexamethylphosphoramide
  3. stirringThe reaction is stirred 30 minutes at 25° C. and 1.5 hour at 105° C.
  4. temperatureby cooling to 25° C
  5. customThe reaction is quenched by addition to 30 ml water
  6. extractionthe mixture extracted with 150 ml ethyl ether
  7. extractionThe ether extract
  8. washis washed twice with 30 ml water, once with 30 ml saturated sodium chloride
  9. dry with materialdried over magnesium sulfate
  10. customevaporated to an oil
  11. customThe crude product is purified via column chromatography on 48 g of silica gel eluting in 8 ml fractions with ethyl ether

Sources & evidence

ORD record
ord-ba3bf8426ac3456f956aad9db66b5dc6
Source dataset
uspto-grants-1985_07
Patent number
US04529732

Reaction notes

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