2-Bromoethanol → (αR,γS)-γ-[[(1,1-Dimethylethoxy)carbonyl]amino]-α-methyl[1,1′-biphenyl]-4-pentanoic acid

HRID 1021055ノート

反応式

HRID 1021055 の反応式
C([O:3][C:4](=[O:30])[C@H:5]([CH3:29])[CH2:6][C@H:7]([NH:21][C:22](=[O:28])[CH2:23][CH2:24][C:25](O)=[O:26])[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.[C:31]1([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH:36]=[CH:35][C:34]([CH2:37][C@@H:38]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:39][C@@H:40]([CH3:44])[C:41]([OH:43])=[O:42])=[CH:33][CH:32]=1.[O:59]=[C:60]([CH3:66])[CH2:61][CH2:62][C:63]([OH:65])=[O:64].S(Cl)(Cl)=O.[Br:71][CH2:72][CH2:73][OH:74]>C1(C)C=CC=CC=1.CN(C)C=O>[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:28])[CH2:23][CH2:24][C:25]([O:74][CH2:73][CH2:72][Br:71])=[O:26])[CH2:6][C@@H:5]([CH3:29])[C:4]([OH:30])=[O:3])=[CH:14][CH:13]=1.[C:31]1([C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH:32]=[CH:33][C:34]([CH2:37][C@@H:38]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:50])[CH3:51])=[O:47])[CH2:39][C@@H:40]([CH3:44])[C:41]([OH:43])=[O:42])=[CH:35][CH:36]=1.[Br:71][CH2:72][CH2:73][O:64][C:63](=[O:65])[CH2:62][CH2:61][C:60](=[O:59])[CH3:66]

参加物

10

反応物 5

HCID 108982-Bromoethanol3 回HCID 11579Levulinic AcidHCID 24386Thionyl ChlorideHCID 9811834SacubitrilHCID 46193546(αR,γS)-γ-[[(1,1-Dimethylethoxy)carbonyl]amino]-α-methyl[1,1′-biphenyl]-4-pentanoic acid

生成物 3

HCID 46193546(αR,γS)-γ-[[(1,1-Dimethylethoxy)carbonyl]amino]-α-methyl[1,1′-biphenyl]-4-pentanoic acidHCID 68710546(2R,4S)-5-Biphenyl-4-yl-4-[3-(2-bromoethoxycarbonyl)propionylamino]-2-methylpentanoic acidHCID 866414854-Oxo-pentanoic acid 2-bromoethyl ester

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

(2R,4S)-5-Biphenyl-4-yl-4-(3-carboxypropionylamino)-2-methylpentanoic acid ethyl ester (3-a, R1=4-oxo-pentanoic acid, R2=H, R3=Et) (5.5 g) is dissolved in toluene (33 ml) at room temperature. Dimethylformamide (0.1 ml) is added. Thionyl chloride (2.4 ml) is then added. The solution is cooled to 0° C. and 2-bromoethanol (0.94 ml) is added. The mixture is stirred at 0° C. for 2 h and then at room temperature for a further 1 h. A further portion of 2-bromoethanol (0.94 ml) is added and the mixture stirred for 0.5 h at room temperature. A further portion of 2-bromoethanol (0.94 ml) is then added and the resulting mixture stirred for 16 h at room temperature. The mixture is concentrated in vacuo to give the crude product. Purification by chromatography Heptane/EtOAc (2:1) gives (2R,4S)-5-Biphenyl-4-yl-4-[3-(2-bromoethoxycarbonyl)propionylamino]-2-methylpentanoic acid (3-a, R1=4-oxo-pentanoic acid 2-bromoethyl ester, R2=H, R3=Et). 1H NMR (DMSO): 1.07 (3H), 1.14 (3H), 1.41 (1H), 1.79 (1H), 2.37 (2H), 2.48 (1H), 2.50 (2H), 2.71 (2H), 3.66 (2H), 3.94 (1H), 3.99 (2H), 4.33 (2H), 7.25 (2H), 7.35 (1H), 7.46 (2H), 7.57 (2H), 7.64 (2H), 7.78 (1H).

後処理

  1. waitat room temperature for a further 1 h
  2. stirringthe mixture stirred for 0.5 h at room temperature
  3. stirringthe resulting mixture stirred for 16 h at room temperature
  4. concentrationThe mixture is concentrated in vacuo
  5. customto give the crude product
  6. customPurification by chromatography Heptane/EtOAc (2:1)

出典と根拠

ORDレコード
ord-cc361415a4a84be593ef9bb5de54d6fc
出典データセット
uspto-grants-2014_05
特許番号
US08716495B2

反応ノート

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