Ethyl Acetate → (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid

HRID 2384022ノート

反応式

HRID 2384022 の反応式
C([O:3][C:4](=[O:31])[C@H:5]([CH3:30])[CH2:6][C@H:7]([NH:21][C:22](=[O:29])[CH2:23][C:24]1[S:25][CH:26]=[CH:27][CH:28]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)C.[OH-].[Na+].C(OCC)(=O)C>C(O)C>[C:12]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:11]=[CH:10][C:9]([CH2:8][C@@H:7]([NH:21][C:22](=[O:29])[CH2:23][C:24]2[S:25][CH:26]=[CH:27][CH:28]=2)[CH2:6][C@@H:5]([CH3:30])[C:4]([OH:31])=[O:3])=[CH:14][CH:13]=1

参加物

5

反応物 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 67506137(2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester

生成物 1

HCID 59608316(2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

Next, to a solution of (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester (0.287 mmol) in ethanol (10 mL) is added aqueous 1M NaOH (2 mL, 6.97 mmol) and the mixture is stirred at room temperature for 18 hours. The mixture is poured into ethyl acetate and is washed with aqueous 1M HCl, the organic phase is dried over magnesium sulfate and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC using a gradient of MeCN/water (0.1% TFA). The proper fractions are lyophilized to furnish (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid. HPLC Retention time 1.23 minutes (condition A); MS 408.3 (M+1); 1H NMR (400 MHz, MeOD-d4) δ ppm 1.16 (d, J=7.07 Hz, 3H), 1.50 (m, 1H), 1.96 (m, 1H), 2.52 (m, 1H), 2.72 (dd, J=7.71 Hz, 7.58 Hz, 1H), 2.84 (dd, J=5.81 Hz, 5.66 Hz, 1H), 3.64 (d, J=1.26 Hz, 2H), 4.20 (m, 1H), 6.82 (m, 1H), 6.89 (m, 1H), 7.21 (m, 3H), 7.32 (m, 1H), 7.42 (m, 2H), 7.46 (m, 2H), 7.57 (m, 2H), 7.95 (d, J=8.59 Hz, 1H).

後処理

  1. washis washed with aqueous 1M HCl
  2. dry with materialthe organic phase is dried over magnesium sulfate
  3. customthe solvent is removed under reduced pressure
  4. customThe residue is purified by preparative HPLC

出典と根拠

ORDレコード
ord-1e724988fbfa43f689e0add007092f28
出典データセット
uspto-grants-2012_09
特許番号
US08263629B2

反応ノート

読み込み中…