Tetrahydrofuran → HCID 178444460, compound

HRID 370693Notes

Reaction equation

HRID 370693 reaction equation
[C:1]([C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][CH2:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:13][CH2:12]2)[CH2:5][CH2:4]1)#[CH:2].O1CCCC1.C([Li])CCC.C1(O[C:39]#[N:40])C=CC=CC=1>CCCCCC.O.CN(C)P(=O)(N(C)C)N(C)C>[C:1]([C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][CH2:10][C@H:11]2[CH2:12][CH2:13][C@H:14]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:15][CH2:16]2)[CH2:5][CH2:4]1)#[CH:2].[CH2:17]([C@H:14]1[CH2:13][CH2:12][C@H:11]([CH2:10][CH2:9][C@H:6]2[CH2:7][CH2:8][C@H:3]([C:1]#[C:2][C:39]#[N:40])[CH2:4][CH2:5]2)[CH2:16][CH2:15]1)[CH2:18][CH2:19][CH2:20][CH3:21]

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 70740Phenyl cyanateHCID 178418339ButyllithiumHCID 178455747HCID 178455747, compound

Product 2

HCID 178444460HCID 178444460, compoundYield 34.8%HCID 178455747HCID 178455747, compoundYield 25.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of 750 mg of trans-1-ethynyl-4-[2-(trans-4-pentylcyclohexyl)ethyl]cyclohexane (prepared according to Example 14) in 75 ml of a 4:1 mixture of absolute tetrahydrofuran and hexamethylphosphoric acid triamide was placed at -45° C. in a sulphonation flask under argon gasification and treated within 2 minutes with 3.3 ml of a 1.0N solution of butyl lithium in hexane. The mixture was subsequently stirred at -20° C. for a further 1 hour, then cooled to -78° C. and treated with 490 μl of phenyl cyanate in a single portion. The mixture was then stirred at -78° C. for a further 2.5 hours, poured into 200 ml of water and extracted three times with 150 ml of diethyl ether each time. The organic phases were washed twice with 150 ml of water each time and once with 100 ml of saturated sodium chloride solution, dried over magnesium sulphate and concentrated. Low-pressure chromatography (0.5 bar) of the residue (2.6 g) on silica gel with hexane gave in sequence 194 mg (25.8%) of trans-1-ethynyl-4-[2-(trans-4-pentylcyclohexyl)ethyl]cyclohexane and 284 mg (34.8%) of trans-4-[2-(trans-4-pentylcyclohexyl)ethyl]cyclohexanepropiolonitrile (purity 98.9%). A recrystallization of the nitrile from methanol yielded colourless crystals (purity 99.4%); m.p. (C-N) 51.4% and cl.p. (N-I) 112.7° C.

Workup

  1. customwas placed at -45° C. in a sulphonation flask under argon
  2. temperaturecooled to -78° C.
  3. stirringThe mixture was then stirred at -78° C. for a further 2.5 hours
  4. extractionextracted three times with 150 ml of diethyl ether each time
  5. washThe organic phases were washed twice with 150 ml of water each time
  6. dry with materialonce with 100 ml of saturated sodium chloride solution, dried over magnesium sulphate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ea82c1da821c4e01b195fdba13a544c0
Source dataset
uspto-grants-1985_07
Patent number
US04528114

Reaction notes

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