(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

반응식

HRID 2036041 반응식
[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]

참가 물질

5

반응물 2

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

생성물 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

시약·촉매·용매 2

HCID 3007855Zincchloride촉매HCID 8028Tetrahydrofuran용매3회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a827ee427a3945fface76942ab9d55a0
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575160B2

연결된 노트

불러오는 중…