Diisopropylethylamine → (R,E)-ethyl 4-(4-(benzyloxy)-1-(3'-chlorobiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobut-2-enoate

HRID 1945020ノート

反応式

HRID 1945020 の反応式
Cl.[NH2:2][C@H:3]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)=[CH:18][CH:17]=1)[CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].[CH2:29]([O:31][C:32](=[O:38])/[CH:33]=[CH:34]/[C:35](O)=[O:36])[CH3:30].CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.O>[CH2:8]([O:7][C:5](=[O:6])[CH2:4][C@H:3]([NH:2][C:35](=[O:36])/[CH:34]=[CH:33]/[C:32]([O:31][CH2:29][CH3:30])=[O:38])[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)=[CH:20][CH:21]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5358902Monoethyl fumarateHCID 86648193(R)-benzyl 3-amino-4-(3'-chlorobiphenyl-4-yl)butanoate hydrochloride

生成物 1

HCID 59607676(R,E)-ethyl 4-(4-(benzyloxy)-1-(3'-chlorobiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobut-2-enoate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To (R)-benzyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate (87.6 mg, 0.183 mmol) is added a solution of HCl in 1,4-dioxane (0.456 mL, 1.825 mmol) at room temperature. After stirring for 3 hours, the reaction mixture is concentrated under reduced pressure to give (R)-benzyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate hydrochloride. A mixture of (R)-benzyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate hydrochloride, fumaric acid monoethyl ester (33.4 mg, 0.220 mmol), EDCl (63.3 mg, 0.330 mmol), DIPEA (0.058 ml, 0.330 mmol) and HOAt (44.9 mg, 0.330 mmol) in DMF (1.8 ml) is allowed to stir at room temperature for 3 hour. The reaction mixture is diluted with water, and then the products are extracted with EtOAc. The organic layer is washed with NH4OH, 1M HClaq and brine, dried over Na2SO4, filtered, and concentrated to give crude. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 0:100) to give (R,E)-ethyl 4-(4-(benzyloxy)-1-(3′-chlorobiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobut-2-enoate (72.9 mg); HPLC retention time=1.40 minutes (condition B); MS (m+1)=506.3; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (t, J=7.1 Hz, 3H) 2.58 (A of ABX, Jab=16.4 Hz, Jax=5.3 Hz, 1H) 2.6 (B of ABX, Jab=16.4 Hz, Jbx=5.1 Hz, 1H) 2.88 (A of ABX, Jab=13.6 Hz, Jax=8.1 Hz, 1H) 3.03 (B of ABX, Jab=13.6 Hz, Jbx=6.3 Hz, 1H) 4.24 (q, J=7.1 Hz, 2H) 4.56-4.64 (m, 1H) 5.12 (A of AB, J=12.1 Hz, 1H) 5.18 (B of AB, J=12.1 Hz, 1H) 6.57 (br d, J=9.1 Hz, 1H) 6.77 (A of AB, J=15.4 Hz, 1H) 6.81 (B of AB, J=15.4 Hz, 1H) 7.19 (br d, J=8.1 Hz, 2H) 7.29-7.47 (m, 10H) 7.53-7.54 (m, 1H).

後処理

  1. extractionthe products are extracted with EtOAc
  2. washThe organic layer is washed with NH4OH, 1M HClaq and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give crude
  7. customThe obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 0:100)

出典と根拠

ORDレコード
ord-3cfa40e966ea4dc7a539dbdb5e01ed08
出典データセット
uspto-grants-2013_03
特許番号
US08394853B2

反応ノート

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