Sodium hydride → (R)-2-[(RS)-2-(2-Bromo-5-fluoro-pyridin-4-yl)-2-(2-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid ethyl ester

HRID 538346노트

반응식

HRID 538346 반응식
[Br:1][C:2]1[CH:7]=[C:6]([C:8]2([CH3:23])[CH2:10][N:9]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N+:20]([O-:22])=[O:21])(=[O:13])=[O:12])[C:5]([F:24])=[CH:4][N:3]=1.[CH2:25]([O:27][C:28](=[O:36])[C@:29]([OH:35])([CH3:34])[C:30]([F:33])([F:32])[F:31])[CH3:26].[H-].[Na+]>CN(C=O)C>[CH2:25]([O:27][C:28](=[O:36])[C@:29]([O:35][CH2:10][C:8]([C:6]1[C:5]([F:24])=[CH:4][N:3]=[C:2]([Br:1])[CH:7]=1)([NH:9][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21])(=[O:13])=[O:12])[CH3:23])([CH3:34])[C:30]([F:31])([F:32])[F:33])[CH3:26]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 26985621(R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionic acid ethyl esterHCID 866680552-Bromo-5-fluoro-4-[2-methyl-1-(2-nitro-benzenesulfonyl)-aziridin-2-yl]-pyridine

생성물 1

HCID 86668056(R)-2-[(RS)-2-(2-Bromo-5-fluoro-pyridin-4-yl)-2-(2-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid ethyl ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 2-bromo-5-fluoro-4-[2-methyl-1-(2-nitro-benzenesulfonyl)-aziridin-2-yl]-pyridine (795 mg, 1.91 mmol) and (R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionic acid ethyl ester (498 mg, 2.67 mmol) in DMF (8 ml, soln. predried over mol. sieves) was added NaH (99 mg of a 60% dispersion in mineral oil, 2.48 mmol) and the reaction mixture was stirred at rt for 3 h. The reaction mixture was quenched with aq. 1N HCl and diluted with H2O and TBME. The phases were separated and the aq. phase was twice extracted with TBME. The combined org. phases were washed with H2O, dried over Na2SO4, filtered and concentrated. Flash chromatography on silica gel (heptane:EtOAc 1:1) yielded the title compound (diastereomer mixture) as a colourless solid. HPLC RtH4=1.26 min; ESIMS: 602, 604 [(M+H)+]; 1H NMR (400 MHz, CDCl3): δ 7.99 (m, 1H), 7.95-7.93 (m, 1H), 7.79-7.61 (m, 4H), 6.94 (m, 1H), 4.45-4.33 (m, 2H), 3.94-3.81 (m, 2H), 1.85 (m, 3H), 1.61 (m, 3H), 1.40-1.34 (m, 3H).

후처리

  1. customThe reaction mixture was quenched with aq. 1N HCl
  2. additiondiluted with H2O and TBME
  3. customThe phases were separated
  4. extractionthe aq. phase was twice extracted with TBME
  5. washphases were washed with H2O
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-5d5e2731491949f29d89b47cec7d19b2
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865712B2

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