Allyl bromide → (3S)-1-allyl-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanol

HRID 527042노트

반응식

HRID 527042 반응식
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C:11](=[O:15])[CH2:10]2)[C:5]([F:16])=[CH:4][N:3]=1.Br[CH2:18][CH:19]=[CH2:20].[NH4+].[Cl-]>CN(C=O)C.[Zn]>[CH2:20]([C:11]1([OH:15])[CH2:12][CH2:13][CH2:14][C@H:9]([NH:8][C:6]2[C:5]([F:16])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:10]1)[CH:19]=[CH2:18]

참가 물질

6

반응물 3

HCID 7841Allyl bromideHCID 25517Ammonium ChlorideHCID 86667417(S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanone2회

생성물 1

HCID 86667442(3S)-1-allyl-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanol

시약·촉매·용매 2

HCID 23994Zinc촉매HCID 6228Dimethylformamide용매

실험 절차

To a solution of (3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]cyclohexanone, 29b, (0.60 g, 2.46 mmol) and 3-bromoprop-1-ene (0.43 mL, 4.92 mmol) in DMF was added Zn dust (0.32 g, 4.92 mmol). The reaction was stirred at room temperature for 3 days. The mixture was diluted into aqueous saturated NH4Cl solution, extracted twice with EtOAc. The combined organic phases were washed twice with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography using 0-50% EtOAc/hexanes gradient to afford 553 mg of desired product, 58a, as an oil. LC/MS two peaks corresponding to two diastereomeric products: 286.4 (M+H), RT=3.41 and 3.78.

후처리

  1. extractionextracted twice with EtOAc
  2. washThe combined organic phases were washed twice with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-94c50de7fba841c08022a52fe446d31f
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345708B2

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