(R)-3-fluoro-4-(7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile → 3-fluoro-4-((5R,7S)-7-hydroxy-7-vinyl-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C@@H:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[C:12](=[O:18])[CH2:11]1)[C:5]#[N:6].[CH:19]([Mg]Br)=[CH2:20]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C@@H:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[C@@:12]([OH:18])([CH:19]=[CH2:20])[CH2:11]1)[C:5]#[N:6]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred solution of 3-fluoro-4-((R)-7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-benzonitrile (0.6 g, 2.5 mmol), in THF (20 mL) cooled in a dry ice acetone bath under nitrogen was added via syringe a solution of vinyl magnesium bromide (0.7 M) in THF (4.3 mL, 3.0 mmol). The crude was warmed to room temperature in 3 hrs. The crude was quenched with NH4Cl aq. The crude was diluted in EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated. The crude was purified via preparation plate using 5% (2M NH3 in MeOH)/CH2Cl2 two times followed by purification using RPHPLC using 10% to 40% MeCN/H2O to give 142 mg of the entitled product as the major diastereomer. MS 270.2 (M+H); LCMS condition A, retention time 0.99 min. 1H NMR (400 MHz, CDCl3-d) ppm 2.56 (br. s., 1H), 2.68 (dd, 1H), 3.22 (dd, 1H), 5.24 (d, 1H), 5.41 (d, 1H), 5.59-5.73 (m, 1H), 6.10 (dd, 1H), 6.91 (br. s., 1H), 7.10 (t, 1H), 7.35 (d, 2H), 7.39 (br. s., 1H).
Workup
- customThe crude was quenched with NH4Cl aq. The crude
- additionwas diluted in EtOAc
- dry with materialThe organic layer was dried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customThe crude was purified via preparation plate
- customfollowed by purification
Sources & evidence
- ORD record
- ord-8ec98856160b41dd82752e22df30581d
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08575160B2
Reaction notes
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