Trimethylaluminum → 3-(4-{[5-(4-Chloro-phenyl)-3-trimethylsilanylethynyl-thiophene-2-carbonyl]-amino}-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

HRID 2384914Notes

Reaction equation

HRID 2384914 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]([NH2:19])=[CH:15][C:14]=2[O:20][CH3:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Al](C)C.C[O:27][C:28]([C:30]1[S:31][C:32]([C:41]2[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=2)=[CH:33][C:34]=1[C:35]#[C:36][Si:37]([CH3:40])([CH3:39])[CH3:38])=O>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:28]([C:30]3[S:31][C:32]([C:41]4[CH:42]=[CH:43][C:44]([Cl:47])=[CH:45][CH:46]=4)=[CH:33][C:34]=3[C:35]#[C:36][Si:37]([CH3:40])([CH3:39])[CH3:38])=[O:27])=[CH:15][C:14]=2[O:20][CH3:21])[CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 46835556Tert-butyl 3-(4-amino-2-methoxyphenoxy)azetidine-1-carboxylateHCID 68953726HCID 68953726, compound

Product 1

HCID 689513263-(4-{[5-(4-Chloro-phenyl)-3-trimethylsilanylethynyl-thiophene-2-carbonyl]-amino}-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Dissolve 3-(4-amino-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (320 mg, 1.09 mmol) in toluene (11 mL) and add 2 M trimethylaluminum (0.65 mL, 1.30 mmol, solution in toluene). Stir the solution at RT for 1 h and then add 5-(4-chloro-phenyl)-3-trimethylsilanylethynyl-thiophene-2-carboxylic acid methyl ester (380 mg, 1.09 mmol). Stir the solution at 50° C. overnight, then carefully quench with saturated Rochelle's salt solution. Stir the mixture for 1 h and then extract with CH2Cl2 (3×30 mL). Combine the organic solutions, dry, filter, and concentrate the filtrate. Purify the crude material by flash chromatography, using 8% MeOH (2 N NH3) in CH2Cl2 as eluent, to give 425 mg (64%) of the title compound as a white solid. LC-MS/ES m/z (35Cl) 555.0 [M−t-butyl+H]+.

Workup

  1. stirringStir the solution at 50° C. overnight
  2. customcarefully quench with saturated Rochelle's salt solution
  3. stirringStir the mixture for 1 h
  4. extractionextract with CH2Cl2 (3×30 mL)
  5. customCombine the organic solutions, dry
  6. filtrationfilter
  7. concentrationconcentrate the filtrate
  8. customPurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-453e1cd76884423cbe4409bdae70660a
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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