p-Toluenesulfonic acid → 1-(2,2-Dimethylpropyl)-5-[(1E)-4-hydroxybut-1-en-1-yl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 629910Notes

Reaction equation

[Si]([O:8][CH2:9][CH2:10]/[CH:11]=[CH:12]/[C:13]1[N:18]=[C:17]2[N:19]([CH3:28])[C:20](=[O:27])[N:21]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:16]2=[CH:15][CH:14]=1)(C(C)(C)C)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:24][C:23]([CH3:26])([CH3:25])[CH2:22][N:21]1[C:16]2[C:17](=[N:18][C:13](/[CH:12]=[CH:11]/[CH2:10][CH2:9][OH:8])=[CH:14][CH:15]=2)[N:19]([CH3:28])[C:20]1=[O:27]

Participants

Conditions

Temperature: 0 °C

Procedure

5-[(1E)-4-{[tert-Butyl(dimethyl)silyl]oxy}but-1-en-1-yl]-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (32-2, 207 mg, 0.51 mmol, 1.0 equiv) was added to anhydrous methanol (5.1 mL) and cooled to 0° C. p-Toluenesulfonic acid (9.7 mg, 0.05 mmol, 0.1 equiv) was added and the resulting solution was stirred at 0° C. for 18 h. Following this duration, LCMS showed complete consumption of 32-2. The contents were diluted ethyl acetate (15 mL) and saturated NaHCO3 (15 mL) and the layers were separated. The aqueous layer was back-extracted with ethyl acetate (3×15 mL) and the combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give a pale yellow oil. Purification by reverse-phase HPLC (10-100% 0.1% TFA in H2O:CH3CN) afforded 32-3 as a colorless oil. MS m/z (M+H): calculated=290.1863; observed=290.1864.

Workup

additionwas added
customconsumption of 32-2
customthe layers were separated
extractionThe aqueous layer was back-extracted with ethyl acetate (3×15 mL)
dry with materialthe combined organics were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customto give a pale yellow oil
customPurification by reverse-phase HPLC (10-100% 0.1% TFA in H2O:CH3CN)

Sources & evidence

ORD record: ord-8c62bf49ad0849a7a986747698ee0bf2
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315518B2

Reaction notes

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