(R)-3-fluoro-4-(7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile → tert-butyl 2-((5R,7S)-5-(4-cyano-2-fluorophenyl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)acetate

HRID 2036041

Reaction equation

HRID 2036041 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].[Cl-].[C:20]([O:24][C:25](=[O:28])[CH2:26][Zn+])([CH3:23])([CH3:22])[CH3:21]>C1COCC1.[Cl-].[Zn+2].[Cl-]>[C:5]([C:4]1[CH:7]=[CH:8][C:9]([C@@H:10]2[N:14]3[CH:15]=[N:16][CH:17]=[C:13]3[C@:12]([CH2:26][C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:28])([OH:18])[CH2:11]2)=[C:2]([F:1])[CH:3]=1)#[N:6]

Participants

5

Reactant 2

HCID 67216150(R)-3-fluoro-4-(7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrileHCID 178451183HCID 178451183, compound

Product 1

HCID 67216546tert-butyl 2-((5R,7S)-5-(4-cyano-2-fluorophenyl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)acetate

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of (R)-3-fluoro-4-(7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile (2.0 g, 8.29 mmol) in THF (40.8 mL) was added a solution of 0.5M (2-tert-butoxy-2-oxoethyl)zinc(II) chloride in THF (39.8 mL, 19.90 mmol). The crude was stirred at room temperature for 2 hrs. To the crude was added and additional 0.5M 2-tert-butoxy-2-oxoethyl)zinc(II) chloride solution in THF (16.6 mL, 8.29 mmol). The crude was stirred at room temperature for 0.5 hr. The crude was quenched with saturated NH4Cl and diluted in EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated. The crude was purified via HPLC 15% to 40% MeCN/H2O, to give 365 mg of the entitled product as the major diastereomer. MS 358.2 (M+H), LCMS condition A, retention time 1.21 min. 1H NMR (400 MHz, CDCl3) δ ppm 1.44 (s, 9H), 2.66-2.74 (m, 1H), 2.76-2.90 (m, 2H), 3.05-3.17 (m, 1H), 5.69 (dd, 1H), 6.96 (s, 1H), 7.12 (t, 1H), 7.31-7.38 (m, 2H), 7.44 (d, 1H).

Workup

  1. additionTo the crude was added
  2. stirringThe crude was stirred at room temperature for 0.5 hr
  3. customThe crude was quenched with saturated NH4Cl
  4. additiondiluted in EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude was purified via HPLC 15% to 40% MeCN/H2O

Sources & evidence

ORD record
ord-a827ee427a3945fface76942ab9d55a0
Source dataset
uspto-grants-2013_11
Patent number
US08575160B2

Linked notes

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