(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

反応式

HRID 2036041 の反応式
[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]

参加物

5

反応物 2

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

生成物 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

試薬・触媒・溶媒 2

HCID 3007855Zincchloride触媒HCID 8028Tetrahydrofuran溶媒3 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-a827ee427a3945fface76942ab9d55a0
出典データセット
uspto-grants-2013_11
特許番号
US08575160B2

関連ノート

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