HCID 688299, 화합물 → HCID 86696675, 화합물

HRID 1774178노트

반응식

HRID 1774178 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][C:3]=1[F:10].CON(C)[C:14]([C@H:16]1[CH2:20][CH2:19][CH2:18][N:17]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:15]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:14]([C@H:16]2[CH2:20][CH2:19][CH2:18][N:17]2[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:15])=[CH:4][C:3]=1[F:10]

참가 물질

4

반응물 2

HCID 688299HCID 688299, 화합물HCID 178505943HCID 178505943, 화합물

생성물 1

HCID 86696675HCID 86696675, 화합물수율 61%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

0.5M (4-Chloro-3-fluorophenyl)magnesium bromide (22.5 mL, 11.2 mmol) as a solution in THF was added dropwise to a cold (0° C.) solution of (R)-tert-butyl 2-(methoxy(methyl)carbamoyl)pyrrolidine-1-carboxylate (1.45 g, 5.61 mmol) in THF (25 mL) under N2, and the reaction was allowed to warm up to room temperature overnight. The next morning, the mixture was placed in an ice bath and carefully quenched with ice. The reaction mixture was concentrated. The residue was treated for 1 hour with a solution of 30% sodium potassium and then extracted with ethyl acetate (2×). The organic layer was dried, filtered and concentrated. The crude product was purified via column chromatography, eluting with hexanes/ethyl acetate (5:1) to give (R)-tert-butyl 2-(4-chloro-3-fluorobenzoyl)pyrrolidine-1-carboxylate (1.12 g, 61%). m/z (APCI-pos) (M+1)-Boc=228.1, 230.1.

후처리

  1. customThe next morning, the mixture was placed in an ice bath
  2. customcarefully quenched with ice
  3. concentrationThe reaction mixture was concentrated
  4. additionThe residue was treated for 1 hour with a solution of 30% sodium potassium
  5. extractionextracted with ethyl acetate (2×)
  6. customThe organic layer was dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified via column chromatography
  10. washeluting with hexanes/ethyl acetate (5:1)

출처 및 근거

ORD 기록
ord-f4bc7d0f868b4be3a58b39e60639b003
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09259470B2

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