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Propylamine hydrochloride → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-[(propylamino)methyl]-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

HRID 505283
ノート
印刷プレビュー

反応式

HRID 505283 の反応式
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[CH2:30]Br)[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:35]([NH2:38])[CH2:36][CH3:37].Cl.CCN(C(C)C)C(C)C>CC#N>[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[CH2:30][NH:38][CH2:35][CH2:36][CH3:37])[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 11165Propylamine hydrochlorideHCID 81531DiisopropylethylamineHCID 57617862(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(bromomethyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

生成物 1

HCID 24896055(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-[(propylamino)methyl]-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

試薬・触媒・溶媒 1

HCID 6342
Acetonitrile
溶媒

反応条件

温度
80 °C

実験手順

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(bromomethyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one (27 mg, 0.0479 mmol) in MeCN (0.5 mL) was added n—PrNH2.HCl (5.5 mg, 0.0575 mmol) and i—Pr2NEt (20.8 μL, 0.120 mmol). The solution was heated at 80° C. for 16 hours. The reaction was then cooled to room temperature and purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA). The fractions containing the desired product were lyophilized to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-[(propylamino)methyl]-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (TFA salt). LCMS=543.1 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 9.72 (s, 2H), 7.90 (s, 1H), 7.76 (s, 2H), 7.72 (d, J=6.9 Hz, 1H), 7.56 (d, J=6.4 Hz, 1H), 7.49 (s, 1H), 5.87 (d, J=7.5 Hz, 1H). 4.98 (d, J=15.3 Hz, 1H), 4.35-4.28 (m, 2H), 4.18 (m, 2H), 3.01 (bs, 2H), 1.75-1.60 (m, 2H), 0.96 (m, 3H), 0.90 (d, J=5.5 Hz, 3H).

後処理

  1. temperatureThe reaction was then cooled to room temperature
  2. custompurified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA)
  3. additionThe fractions containing the desired product

出典と根拠

ORDレコード
ord-234e27fdd29644119f7bb0b9d4a1ef60
出典データセット
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07781426B2

反応ノート

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