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 538346ノート

反応式

HRID 538346 の反応式
[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]

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-5d5e2731491949f29d89b47cec7d19b2
出典データセット
uspto-grants-2014_10
特許番号
US08865712B2

反応ノート

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