Tetrabutylammonium Fluoride → 3-{4-[2-(4-Chloro-phenyl)-7-oxo-7H-thieno[2,3-c]pyridin-6-yl]-2-methoxy-phenoxy}-azetidine-1-carboxylic acid tert-butyl ester

HRID 2384915Notes

Reaction equation

HRID 2384915 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]3[S:23][C:24]([C:33]4[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=4)=[CH:25][C:26]=3[C:27]#[C:28][Si](C)(C)C)=[O:21])=[CH:15][C:14]=2[O:40][CH3:41])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:28]=[CH:27][C:26]4[CH:25]=[C:24]([C:33]5[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=5)[S:23][C:22]=4[C:20]3=[O:21])=[CH:15][C:14]=2[O:40][CH3:41])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 689513263-(4-{[5-(4-Chloro-phenyl)-3-trimethylsilanylethynyl-thiophene-2-carbonyl]-amino}-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 689482573-{4-[2-(4-Chloro-phenyl)-7-oxo-7H-thieno[2,3-c]pyridin-6-yl]-2-methoxy-phenoxy}-azetidine-1-carboxylic acid tert-butyl esterYield 75.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve 3-(4-{[5-(4-chloro-phenyl)-3-trimethylsilanylethynyl-thiophene-2-carbonyl]-amino}-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (420 mg, 0.69 mmol) in THF (11 mL) and add 1 M tetrabutylammonium fluoride (1.50 mL, 1.50 mmol, solution in THF). Stir the solution at RT overnight. Dilute the solution with EtOAc (100 mL) and wash with water (3×50 mL) and brine (50 mL). Dry the organic solution, filter, and concentrate the filtrate. Purify the crude material by flash chromatography, using a linear gradiant of 30-70% EtOAc/hexanes, to give 280 mg (75%) of the title compound. LC-MS/ES m/z (35Cl) 483.0 [M−t-butyl+H]+.

Workup

  1. washwash with water (3×50 mL) and brine (50 mL)
  2. customDry the organic solution
  3. filtrationfilter
  4. concentrationconcentrate the filtrate
  5. customPurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-826a8ea5b81942c8a80f93c9d64b3b65
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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