Hydrochloric Acid → [6-Ethynyl-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1517091Notes

Reaction equation

HRID 1517091 reaction equation
[CH3:1][C:2]1[C:3]([C:24]([N:26]2[CH2:31][CH2:30][CH:29]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)[CH2:28][CH2:27]2)=[O:25])=[N:4][C:5]([C:18]#[C:19][Si](C)(C)C)=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CCO.C1COCC1>[C:18]([C:5]1[N:4]=[C:3]([C:24]([N:26]2[CH2:31][CH2:30][CH:29]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)[CH2:28][CH2:27]2)=[O:25])[C:2]([CH3:1])=[CH:7][C:6]=1[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:16])([F:17])[F:15])[CH:9]=1)#[CH:19]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 57441155[3-Methyl-5-(3-trifluoromethyl-phenyl)-6-trimethylsilanylethynyl-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone2×

Product 1

HCID 57441142[6-Ethynyl-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 79%

Reagents, catalysts & solvents 1

HCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

A solution of 0.65 g (1.27 mmol) of [3-methyl-5-(3-trifluoromethyl-phenyl)-6-trimethylsilanylethynyl-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (intermediate 12) in 12 ml of EtOH/THF (5:1) was treated at RT with 0.35 g (2.53 mmol) of potassium carbonate. After 4 hours, the reaction mixture was poured into crashed ice, the pH was adjusted to 3-4 with hydrochloric acid (2 molar) and the mixture was extracted three times with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1) to give 0.439 g (79%) of the title compound as brown solid. MS: 442.3 (MH+).

Workup

  1. additionthe reaction mixture was poured
  2. extractionthe mixture was extracted three times with CH2Cl2
  3. washthe organic phases were washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1)

Sources & evidence

ORD record
ord-bf64054380584fe2bbf89fa59e2eefa2
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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