Cyclohexyl isocyanide → HCID 178455701, compound

HRID 1510160Notes

Reaction equation

HRID 1510160 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[C:7]([CH:18]=[CH:19][CH:20]=1)[CH2:8][N:9]1[CH2:14][CH2:13][C:12](=O)[CH2:11][CH:10]1[CH:16]=[CH2:17])([CH3:3])[CH3:2].[CH:21]1([N+:27]#[C-:28])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.[O-:29][C:30]#[N:31].[K+].Cl.[F:34][C:35]1[CH:36]=[C:37]([CH:39]=[CH:40][CH:41]=1)[NH2:38]>CO.O>[CH:21]1([NH:27][C:28]2[C@:12]3([CH2:13][CH2:14][N:9]([CH2:8][C:7]4[CH:18]=[CH:19][CH:20]=[C:5]([O:4][CH:1]([CH3:3])[CH3:2])[CH:6]=4)[C@@H:10]([CH:16]=[CH2:17])[CH2:11]3)[N:38]([C:37]3[CH:39]=[CH:40][CH:41]=[C:35]([F:34])[CH:36]=3)[C:30](=[O:29])[N:31]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

7

Reactant 4

HCID 79129Cyclohexyl isocyanide2×HCID 27557653-Fluorophenylamine hydrochloride2×HCID 11378442Potassium cyanate2×HCID 66790112HCID 66790112, compound

Product 1

HCID 178455701HCID 178455701, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

1-(3-isopropoxybenzyl)-2-vinylpiperidin-4-one (7.00 g, 25.6 mmol) in methanol (14 ml) was added cyclohexyl isocyanide (3.17 ml, 25.6 mmol) then potassium cyanate (2.08 g, 25.6 mmol) in water (5 ml) was added. 3-Fluoroaniline hydrochloride (3.78 g, 25.6 mmol) was then added at 0° C. The mixture was stirred at rt for 12 hrs. The reaction was incomplete and another half equivalent of cyclohexyl isocyanide (1.59 ml, 12.8 mmol), potassium cyanate (1.04 g, 12.8 mmol), and 3-fluoroaniline hydrochloride (1.89 g, 12.8 mmol) was added. The mixture stirred for an additional twelve hours. The solution was concentrated and purified on silica gel 7% methanol/chloroform with 0.1% triethylamine. The impure product was purified a second time by flash chromatography on silica gel starting with 50% ethyl acetate/hexanes to 100% ethyl acetate. The diastereomers were resolved on a Chiral AD column 10% ethanol/hexanes with 0.3% diethylamine 250 ml/min at 250 nm.

Workup

  1. stirringThe mixture stirred for an additional twelve hours
  2. concentrationThe solution was concentrated
  3. custompurified on silica gel 7% methanol/chloroform with 0.1% triethylamine
  4. customThe impure product was purified a second time by flash chromatography on silica gel starting with 50% ethyl acetate/hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-d57fd99f377a42fe926833ef7ecc89ab
Source dataset
uspto-grants-2012_07
Patent number
US08211904B2

Reaction notes

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