Citric Acid → (2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

HRID 1500446노트

반응식

HRID 1500446 반응식
Cl.[CH2:2]([O:4][C:5](=[O:24])[C@@H:6]([CH3:23])[CH2:7][C@H:8]([NH2:22])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)[CH3:3].[C:25]1([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:30]=[CH:29][C:28]([CH2:31][C@@H:32]([NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:33][C@@H:34]([CH3:38])[C:35]([OH:37])=[O:36])=[CH:27][CH:26]=1.[C:53](Cl)(=[O:58])[C:54]([CH3:57])([CH3:56])[CH3:55].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(OC(C)C)(=O)C.O.C(N(CC)CC)C>[CH2:2]([O:4][C:5](=[O:24])[C@H:6]([CH3:23])[CH2:7][C@H:8]([NH:22][C:53](=[O:58])[C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:14][CH:15]=1)[CH3:3].[C:25]1([C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:26]=[CH:27][C:28]([CH2:31][C@@H:32]([NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:44])[CH3:45])=[O:41])[CH2:33][C@@H:34]([CH3:38])[C:35]([OH:37])=[O:36])=[CH:29][CH:30]=1

참가 물질

9

반응물 4

HCID 311Citric AcidHCID 62493Pivaloyl chlorideHCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acidHCID 66739279HCID 66739279, 화합물

생성물 2

HCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acidHCID 66739227HCID 66739227, 화합물

시약·촉매·용매 3

HCID 962Water용매HCID 7915Isopropyl Acetate용매3회HCID 8471Triethylamine용매

실험 절차

10 g (2S,4S)-4-amino-5-biphenyl-4-yl-2-methylpentanoic acid ethyl ester hydrochloride (3-a, R1=R2=H, R3=Et) in isopropyl acetate (50 ml) is added to a mixture of pivaloyl chloride (4.1 ml) in isopropyl acetate (50 ml). The mixture is then stirred for 40 min at room temperature. Triethylamine (10.3 ml) in isopropyl acetate (30 ml) is then added over a period of 1 h. The resulting mixture is stirred for 16 h. Citric acid (7.5 g) dissolved in water (30 ml) is added and the phases are separated. The organic phase is washed twice with water (30 ml) and concentrated in vacuo to give (2R,4S)-5-Biphenyl-4-yl-4-(2,2-dimethylpropionylamino)-2-methylpentanoic acid ethyl ester (3-a, R1=Piv, R2=H, R3=Et). 1H NMR (DMSO): 1.05 (9H), 1.09 (3H), 1.15 (3H), 1.54 (1H), 1.78 (1H), 2.48 (1H), 2.72 (2H), 3.97 (1H), 4.00 (2H), 7.15 (1H), 7.25 (2H), 7.34 (1H), 7.45 (2H), 7.55 (2H), 7.62 (2H).

후처리

  1. stirringThe resulting mixture is stirred for 16 h
  2. additionis added
  3. customthe phases are separated
  4. washThe organic phase is washed twice with water (30 ml)
  5. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-c8f5210038fd41af99f9e6e577c67a4e
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206116B2

반응 노트

불러오는 중…