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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
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HRID 2384036 반응식
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
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참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol
용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-14fb3653cee14a5b8b236603ff2a6d3a
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08263629B2

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