Ammonium fluoride → 4-Hydroxymethyl-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone

HRID 21226

Reaction equation

FC(F)(F)S(O[C:7]1[CH:15]=[CH:14][C:13]([C:16]2[N:17]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:18]3[C:23]([CH:24]=2)=[CH:22][C:21]([CH2:25][N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:20][CH:19]=3)=[C:12]2[C:8]=1[CH2:9][NH:10][C:11]2=[O:39])(=O)=O.[OH:42][CH2:43][Sn](CCCC)(CCCC)CCCC.[F-].[NH4+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:42][CH2:43][C:7]1[CH:15]=[CH:14][C:13]([C:16]2[N:17]([C:32]([O:34][C:35]([CH3:37])([CH3:38])[CH3:36])=[O:33])[C:18]3[C:23]([CH:24]=2)=[CH:22][C:21]([CH2:25][N:26]2[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]2)=[CH:20][CH:19]=3)=[C:12]2[C:8]=1[CH2:9][NH:10][C:11]2=[O:39]

Participants

Conditions

Temperature: 90 °C

Procedure

4-Trifluoromethanesulfonyloxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (80.0 mg, 0.135 mmol) was dissolved in 1,4-dioxane (2.4 mL), and the solution was added with hydroxymethyltributyltin (87 mg, 0.27 mmol) synthesized in a similar manner to the method described in Synthetic Communications, 1994, vol. 24, p. 1117, and tetrakis(triphenylphosphine)palladium (12.5 mg, 0.0108 mmol), followed by stirring at 90° C. for 2.7 hours under argon atmosphere. The mixture was further added with tetrakis(triphenylphosphine)palladium (6.3 mg, 0.054 mmol) and stirred for 2.3 hours. Further, the mixture was added with hydroxymethyltributyltin (44 mg, 0.14 mmol), tetrakis(triphenylphosphine)palladium (6.3 mg, 0.0054 mmol) and 1,4-dioxane (1.2 mL), followed by stirring for 4 hours. The reaction mixture was added with 10% aqueous ammonium fluoride solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by preparative thin-layer chromatography (chloroform/methanol=10/1) to obtain 4-hydroxymethyl-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (15.0 mg, yield 23%).

Workup

customsynthesized in a similar manner to the method
stirringstirred for 2.3 hours
stirringby stirring for 4 hours
extractionextracted with ethyl acetate
washThe organic layer was washed with saturated brine
dry with materialdried over sodium sulfate
customThe solvent was evaporated under reduced pressure
customThe residue was purified by preparative thin-layer chromatography (chloroform/methanol=10/1)

Sources & evidence

ORD record: ord-3ed82f58fc664bd8a32be65ff7c6d5e5
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745641B2

Linked notes

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