Tetrahydrofuran → HCID 58046540, compound

HRID 706358Notes

Reaction equation

HRID 706358 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:15][CH2:14][N:13]([CH2:16]/[CH:17]=[CH:18]/[C:19]4[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=4)[CH2:12][CH2:11]3)[CH2:9][NH:8][C:5]2=[CH:6][CH:7]=1.[CH2:26]1[CH2:30][O:29][CH2:28][CH2:27]1>>[C:5]([C:4]1[CH:28]=[CH:27][C:26]([C:30]([N:8]2[C:5]3[C:4](=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=3)[C:10]3([CH2:15][CH2:14][N:13]([CH2:16]/[CH:17]=[CH:18]/[C:19]4[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=4)[CH2:12][CH2:11]3)[CH2:9]2)=[O:29])=[CH:2][CH:3]=1)#[N:8]

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 58046573HCID 58046573, compound

Product 1

HCID 58046540HCID 58046540, compound

Procedure

This step was achieved using a Zymark XP2 synthetic chemistry robot. A solution of 5-methyl-1′-[trans-3-(4-chlorophenyl)allyl]spiro[indoline-3,4′-piperidine] (2 ml of a solution derived from dissolving 1.43 g in 100 ml of THF) was added to a robot tube and the solvent was removed in vacuo. 4-Cyanobenzoic acid (28 mg) was weighed into a different robot tube. A solution of 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate (2 ml of a solution derived from dissolving 4.80 g in 180 ml of chloroform) and a solution of triethylamine (2 ml of a solution derived from dissolving 8.68 ml in 250 ml of chloroform) were added to the acid and the tube was agitated and allowed to stand for 30 minutes. A 2 ml aliquot of the acid solution was added to the tube containing the dry amine. This tube was agitated and allowed to stand overnight. The reaction mixture was washed with 1M aqueous sodium carbonate solution and the solvents were evaporated. The crude mixture was purified by MS directed liquid chromatography to give the desired amide, 2.9 mg. MS (ES+) 482/484 (M+H+).

Workup

  1. additionwas added to a robot tube
  2. customthe solvent was removed in vacuo
  3. custom4-Cyanobenzoic acid (28 mg) was weighed into a different robot tube
  4. dissolutionA solution of 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate (2 ml of a solution derived from dissolving 4.80 g in 180 ml of chloroform)
  5. dissolutiona solution of triethylamine (2 ml of a solution derived from dissolving 8.68 ml in 250 ml of chloroform)
  6. additionwere added to the acid
  7. additionA 2 ml aliquot of the acid solution was added to the tube
  8. additioncontaining the dry amine
  9. stirringThis tube was agitated
  10. waitto stand overnight
  11. washThe reaction mixture was washed with 1M aqueous sodium carbonate solution
  12. customthe solvents were evaporated
  13. customThe crude mixture was purified by MS

Sources & evidence

ORD record
ord-7d31aae8d86b4adcb0cc736c0d53b7ba
Source dataset
uspto-grants-2015_11
Patent number
US09174987B2

Reaction notes

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