1,2-Diaminocyclohexane, trans- → (S)-tert-butyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407880노트

반응식

HRID 407880 반응식
Br[C:2]1[CH:27]=[CH:26][C:5]([O:6][C@H:7]2[CH2:11][CH2:10][N:9]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[C:8]2=[O:25])=[C:4]([F:28])[CH:3]=1.[CH3:29][S:30]([O-:32])=[O:31].[Na+].[C@@H]1(N)CCCC[C@H]1N>CS(C)=O>[F:28][C:4]1[CH:3]=[C:2]([S:30]([CH3:29])(=[O:32])=[O:31])[CH:27]=[CH:26][C:5]=1[O:6][C@H:7]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[C:8]1=[O:25]

참가 물질

5

반응물 3

HCID 438061,2-Diaminocyclohexane, trans-HCID 2733271Sodium methanesulfinateHCID 86688077(S)-tert-butyl 4-(3-(4-bromo-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

생성물 1

HCID 86688078(S)-tert-butyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate수율 89.7%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

(S)-tert-Butyl 4-(3-(4-bromo-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (1.8 g, 3.9 mmol) was dissolved in DMSO (30 mL) and purged with nitrogen. Sodium methanesulfinate (0.60 g, 5.9 mmol) and trans-cyclohexane-1,2-diamine (0.19 mL, 1.6 mmol) were added followed by Cu(I) triflate benzene complex (0.20 g, 0.39 mmol). The reaction was plunged into a 110° C. oil bath under nitrogen and stirred overnight. The reaction was cooled to ambient temperature, partitioned between water and EtOAc, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (100% EtOAc) to afford (S)-tert-butyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (1.6 g, 3.5 mmol, 89% yield) as a white solid.

후처리

  1. custompurged with nitrogen
  2. customwas plunged into a 110° C.
  3. custompartitioned between water and EtOAc
  4. extractionextracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified over silica gel (100% EtOAc)

출처 및 근거

ORD 기록
ord-b4e02b39efcb48069e57305ec78b7e96
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754226B2

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