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Sodium Carbonate → (R)-tert-butyl 4-(4-ethoxy-1-(5'-fluoro-2'-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate

HRID 70825
ノート
印刷プレビュー

反応式

HRID 70825 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:16][C:17](=[O:27])[CH2:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:4][CH:3]=1.[F:28][C:29]1[CH:30]=[CH:31][C:32]([O:38][CH3:39])=[C:33](B(O)O)[CH:34]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:14]([O:13][C:11](=[O:12])[CH2:10][C@H:9]([NH:16][C:17](=[O:27])[CH2:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:31]2[CH:30]=[C:29]([F:28])[CH:34]=[CH:33][C:32]=2[O:38][CH3:39])=[CH:3][CH:4]=1)[CH3:15]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 59607774(R)-tert-butyl 4-(1-(4-bromophenyl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoate

生成物 1

HCID 67208801(R)-tert-butyl 4-(4-ethoxy-1-(5'-fluoro-2'-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate

試薬・触媒・溶媒 3

HCID 178418397
HCID 178418397、化合物
触媒
HCID 702Ethanol溶媒
HCID 1140Toluene溶媒

反応条件

温度
95 °C

実験手順

To a solution of (R)-tert-butyl 4-(1-(4-bromophenyl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoate, intermediate 9, (100 mg, 0.23 mmol) and 5-fluoro-2-methoxyphenylboronic acid (57.6 mg, 0.34 mmol) in toluene (1 mL) and EtOH (0.1 mL) is added Pd(PPh3)4 (26.1 mg, 0.023 mmol) and Na2CO3 (47.9 mg, 0.45 mmol). After stirring at 95° C. under nitrogen for 18 hours, the solution is cooled to ambient temperature and then quenched with aqueous 1 M HCl. 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 30:70) to give (R)-tert-butyl 4-(4-ethoxy-1-(5′-fluoro-2′-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate (65 mg). HPLC retention time=1.44 minutes (condition B); MS (m+1)=488.3; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (t, J=7.1 Hz, 3 H) 1.48 (s, 9 H) 2.41-2.48 (m, 2 H) 2.51-2.63 (m, 4 H) 2.90 (dd, J=13.6, 6 Hz, 1 H) 3.02 (dd, J=13.6, 6 Hz, 1 H) 3.81 (s, 3 H) 4.14-4.29 (m, 2 H) 4.49-4.63 (m, 1 H) 6.44 (d, J=8.6 Hz, 1 H) 6.89-6.97 (m, 1 H) 6.98-7.05 (m, 1 H) 7.05-7.11 (m, 1 H) 7.27 (d, J=8.1 Hz, 2 H) 7.49 (d, J=8.1 Hz, 2 H).

後処理

  1. temperaturethe solution is cooled to ambient temperature
  2. customquenched with aqueous 1 M HCl
  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 30:70)

出典と根拠

ORDレコード
ord-2a7566d6ee1f4475bfed1307cb623dce
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08822534B2

反応ノート

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