Diisopropylethylamine → 6-{(SR)-1-[(3RS,4SR)-4-(4-Cyano-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile

HRID 559291Notes

Reaction equation

C([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][CH:14]=2)[CH:10]([CH:21]([O:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=2)[CH3:22])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[C:19]([C:16]1[CH:15]=[CH:14][C:13]([CH:11]2[CH2:12][NH:8][CH2:9][CH:10]2[CH:21]([O:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=2)[CH3:22])=[CH:18][CH:17]=1)#[N:20]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 6-{(SR)-1-[(3RS,4SR)-1-benzyl-4-(4-cyano-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile (VI-B-5) 380 mg (0.93 mmol) dissolved in toluene (10 mL) were added 0.30 mL (2.79 mmol) of 1-chloroethyl chloroformate and 0.47 mL (2.79 mmol) of Hunig's base. The reaction mixture was heated at 100° C. for one hour. After cooling down to RT, volatiles were removed under vacuo and the crude was dissolved in MeOH (10 mL). The reaction mixture was heated at 85° C. for 30 minutes and after cooling down to RT, volatiles were removed under vacuo and the residue was directly purified on column chromatography (SiO2, CH2Cl2/MeOH 9:1) yielded 105 mg (35%) of the title compound as a light yellow oil. ES-MS m/e: 319.2 (M+H+).

Workup

temperatureAfter cooling down to RT
customvolatiles were removed under vacuo
dissolutionthe crude was dissolved in MeOH (10 mL)
temperatureThe reaction mixture was heated at 85° C. for 30 minutes
temperatureafter cooling down to RT
customvolatiles were removed under vacuo
customthe residue was directly purified on column chromatography (SiO2, CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record: ord-97691c9181a54fa8b82cc657d98c50af
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063075B2

Reaction notes

Loading…