Ethyl 4-piperidinecarboxylate → Ethyl 1-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)piperidine-4-carboxylate

HRID 17428

Reaction equation

HRID 17428 reaction equation
Cl[C:2]1[O:3][C:4]2[C:5](=[C:7]([C:19]#[N:20])[C:8]([CH3:18])=[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:10]=2[F:11])[N:6]=1.[NH:21]1[CH2:31][CH2:30][CH:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:23][CH2:22]1.C(N(C(C)C)CC)(C)C>ClCCl>[C:19]([C:7]1[C:5]2[N:6]=[C:2]([N:21]3[CH2:31][CH2:30][CH:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:23][CH2:22]3)[O:3][C:4]=2[C:10]([F:11])=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]=1[CH3:18])#[N:20]

Participants

5

Reactant 3

HCID 70770Ethyl 4-piperidinecarboxylateHCID 81531DiisopropylethylamineHCID 510414292-Chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

Product 1

HCID 68584803Ethyl 1-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)piperidine-4-carboxylateYield 94.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-Chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-130) (0.20 g, 0.70 mmol) was dissolved in dichloromethane (10 ml), then ethyl isonipecotate (0.12 ml, 0.78 mmol) and diisopropylethylamine (0.15 ml, 0.88 mmol) were added, followed by heating under reflux for 3 hours. This was diluted with dichloromethane, washed with water, and dried over anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified by silica gel column chromatography (dichloromethane:methanol=100:1) to obtain a yellow oil (0.27 g, 94%).

Workup

  1. temperatureby heating
  2. temperatureunder reflux for 3 hours
  3. washwashed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated away under reduced pressure
  6. customthe resulting residue was purified by silica gel column chromatography (dichloromethane:methanol=100:1)

Sources & evidence

ORD record
ord-c621a90cb5f249d28996c6376a931ddc
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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