Diisopropylethylamine → (R)-tert-butyl 3-(biphenyl-4-ylmethyl)-4-(3-methoxy-3-oxopropylamino)-4-oxobutanoate

HRID 1945041

反応式

HRID 1945041 の反応式
[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:9](O)=[O:10])=[CH:3][CH:2]=1.Cl.[CH3:27][O:28][C:29](=[O:33])[CH2:30][CH2:31][NH2:32].CCN=C=NCCCN(C)C.Cl.ON1C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:8]([C:9]([NH:32][CH2:31][CH2:30][C:29]([O:28][CH3:27])=[O:33])=[O:10])[CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:5][CH:6]=1

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 59607655(R)-2-(biphenyl-4-ylmethyl)-4-tert-butoxy-4-oxobutanoic acid

生成物 1

HCID 59607897(R)-tert-butyl 3-(biphenyl-4-ylmethyl)-4-(3-methoxy-3-oxopropylamino)-4-oxobutanoate収率 92.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of (R)-2-(biphenyl-4-ylmethyl)-4-tert-butoxy-4-oxobutanoic acid (142 mg, 0.417 mmol), 3-amino-propionic acid methyl ester hydrochloride (76 mg, 0.542 mmol), WSC hydrochloride (120 mg, 0.626 mmol), 1-hydroxy-7-azabenzotriazole (85 mg, 0.626 mmol) and DIPEA (0.219 ml, 1.251 mmol) in DMF (4 mL) is allowed to stir at room temperature under nitrogen for 13 hours. The reaction is quenched with H2O. The products are extracted with ethyl acetate, washed with aqueous 1M HCl and then with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by flash column chromatography on 12 g of silica gel (heptane/EtOAc=70:30 to 0:100) to give (R)-tert-butyl 3-(biphenyl-4-ylmethyl)-4-(3-methoxy-3-oxopropylamino)-4-oxobutanoate (164 mg, 91%). HPLC retention time=1.59 minutes (condition A); MS (ES+)=425.4 (m); 369.4 (m-tBu+1; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.24-2.44 (m, 2H) 2.67-2.79 (m, 3H) 2.89-2.96 (m, 1H) 3.28-3.36 (m, 1H) 3.45-3.53 (m, 1H) 7.23 (d, J=5.8 Hz, 2H) 7.33 (t, J=7.35 Hz, 1H) 7.41-7.44 (m, 2H) 7.51 (d, J=8.1 Hz, 2H) 7.58 (d, J=7.4 Hz, 2H).

後処理

  1. customThe reaction is quenched with H2O
  2. extractionThe products are extracted with ethyl acetate
  3. washwashed with aqueous 1M HCl
  4. dry with materialwith brine, dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue is purified by flash column chromatography on 12 g of silica gel (heptane/EtOAc=70:30 to 0:100)

出典と根拠

ORDレコード
ord-79d31949f4474be680ba97494bf062ea
出典データセット
uspto-grants-2013_03
特許番号
US08394853B2

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