Sodium Carbonate → (R)-ethyl 3-(tert-butoxycarbonylamino)-4-(5'-fluoro-2'-methoxybiphenyl-4-yl)butanoate

HRID 1945065

反応式

HRID 1945065 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:4][CH:3]=1.[F:24][C:25]1[CH:26]=[CH:27][C:28]([O:34][CH3:35])=[C:29](B(O)O)[CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[C:20]([O:19][C:17]([NH:16][C@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:27]2[CH:26]=[C:25]([F:24])[CH:30]=[CH:29][C:28]=2[O:34][CH3:35])=[CH:3][CH:4]=1)[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:18])([CH3:23])([CH3:22])[CH3:21]

参加物

5

反応物 3

HCID 10340Sodium CarbonateHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 59607624(R)-Ethyl 4-(4-bromophenyl)-3-((tert-butoxycarbonyl)amino)butanoate

生成物 1

HCID 59607779(R)-ethyl 3-(tert-butoxycarbonylamino)-4-(5'-fluoro-2'-methoxybiphenyl-4-yl)butanoate収率 82%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
95 °C

実験手順

To a solution of (R)-ethyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate, (3.12 g, 8.08 mmol), and 5-fluoro-2-methoxyphenylboronic acid (2.2 g, 12.93 mmol) in toluene (52 mL) and is added PdCl2(dppf)CH2Cl2 adduct (0.66 g, 0.81 mmol) and 2M aq. Na2CO3 (8.1 mL, 16.16 mmol). After stirring at 95° C. under nitrogen for 4 hours, the solution is cooled to ambient temperature and then quenched with ice water. The crude is diluted with ethyl acetate. The organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 50:50) to give (R)-ethyl 3-(tert-butoxycarbonylamino)-4-(5′-fluoro-2′-methoxybiphenyl-4-yl)butanoate (2.86 g). HPLC retention time=1.80 minutes (condition A); MS (m+1)=432.2; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (t, J=7.1 Hz, 3H) 1.45 (s, 9H) 2.45-2.65 (m, 2H) 2.83-2.94 (m, 1H) 2.94-3.09 (m, 1H) 3.80 (s, 3H) 4.20 (q, J=7.2 Hz, 2H) 4.24-4.33 (m, 1H) 5.11 (br. s., 1H) 6.90-6.96 (m, 1H) 7.00 (dd, J=7.8, 3.3 Hz, 1H) 7.06 (dd, J=9.2, 3.2 Hz, 1H) 7.27 (d, J=7.8 Hz, 2H) 7.49 (d, J=7.8 Hz, 2H)

後処理

  1. temperaturethe solution is cooled to ambient temperature
  2. customquenched with ice water
  3. additionThe crude is diluted with ethyl acetate
  4. washThe organic layer is washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue is purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 50:50)

出典と根拠

ORDレコード
ord-2790fbe510cb4d169c627b702c91c3cf
出典データセット
uspto-grants-2013_03
特許番号
US08394853B2

関連ノート

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