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Hydrochloric Acid → (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid

HRID 2384036
ノート
印刷プレビュー

反応式

HRID 2384036 の反応式
C([O:3][C:4](=[O:34])[C@H:5]([CH3:33])[CH2:6][C@H:7]([NH:21][C:22](=[O:32])[C:23]1[CH:28]=[C:27]([F:29])[C:26]([OH:30])=[C:25]([F:31])[CH:24]=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+].Cl>CO>[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:32])[C:23]2[CH:28]=[C:27]([F:29])[C:26]([OH:30])=[C:25]([F:31])[CH:24]=2)[CH2:6][C@@H:5]([CH3:33])[C:4]([OH:34])=[O:3])=[CH:14][CH:13]=1
参加物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 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67506121(2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid ethyl ester

生成物 1

HCID 59608305(2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid収率 60.8%

試薬・触媒・溶媒 1

HCID 887Methanol
溶媒

実験手順

Next, to a solution of (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid ethyl ester (30 mg, 0.064 mmol) in MeOH (2 mL) at room temperature is added aqueous 1M NaOH (4 mL, 4.0 mmol). After stirring for 1 hour the reaction is quenched with aqueous 1M HCl (4 mL, 4.0 mmol). The mixture is concentrated under reduced pressure and filtered to remove NaCl salt. The obtained residue is purified by preparative silica gel thin-layer chromatography (7% MeOH in DCM) to give 17.1 mg of (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid. HPLC Retention time 1.56 minutes (condition B); MS 440 (M+1); 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 1.19 (d, J=7.07 Hz, 3H) 1.55 (ddd, J=14.27, 10.74, 3.79 Hz, 1H) 1.90-1.96 (m, 1H) 2.54-2.71 (m, 1H) 2.91 (dd, J=6.69, 3.16 Hz, 2H) 4.25-4.43 (m, 1H) 6.49 (d, J=9.60 Hz, 2H) 6.93 (d, J=8.84 Hz, 1H) 7.33-7.42 (m, 3H) 7.49 (t, J=7.71 Hz, 2H) 7.61 (d, J=8.34 Hz, 2H) 7.67 (dd, J=8.34, 1.26 Hz, 2H).

後処理

  1. concentrationThe mixture is concentrated under reduced pressure
  2. filtrationfiltered
  3. customto remove NaCl salt
  4. customThe obtained residue is purified by preparative silica gel thin-layer chromatography (7% MeOH in DCM)

出典と根拠

ORDレコード
ord-14fb3653cee14a5b8b236603ff2a6d3a
出典データセット
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08263629B2

反応ノート

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