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

HRID 1641664ノート

反応式

HRID 1641664 の反応式
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

参加物

9

反応物 4

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

生成物 2

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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 7915Isopropyl Acetate溶媒3 回HCID 8471Triethylamine溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-a0db875b6c464e4faaea14788113e344
出典データセット
uspto-grants-2012_02
特許番号
US08115016B2

反応ノート

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