Sodium Carbonate → (R)-ethyl 4-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)butanoate

HRID 70859

反応式

HRID 70859 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.[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:3][CH:4]=1)[CH3:15]

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 59607624(R)-Ethyl 4-(4-bromophenyl)-3-((tert-butoxycarbonyl)amino)butanoate

生成物 1

HCID 59607632(R)-ethyl 4-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)butanoate収率 87.4%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 1140Toluene溶媒

反応条件

温度
95 °C

実験手順

A mixture of (R)-ethyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (1.5 g, 3.88 mmol), phenylboronic acid (0.710 g, 5.82 mmol), Pd(Ph3P)4 (0.449 g, 0.388 mmol) and aqueous Na2CO3 (3.88 mL, 7.77 mmol) in toluene (25 mL) is allowed to stir at 95° C. under nitrogen for 14 hours. The reaction mixture is cooled to room temperature and quenched with brine. The mixture is extracted twice with ethylacetate, and the combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 50:50) to give (R)-ethyl-4-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)butanoate (1.30 g); HPLC retention time=1.61 minutes (condition B); MS (ES+)=328.0 (m-tBu+2); 284.1 (m-Boc+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.28 (t, J=7.1 Hz, 3 H) 2.48 (A of ABX, Jab=16.1 Hz, Jax=5.9 Hz, 1 H) 2.53 (B of ABX, Jab=16.0 Hz, Jbx=5.3 Hz, 1 H) 2.83-3.00 (m, 2 H) 4.14-4.19 (m, 3 H) 5.06 (br s) 7.26-7.27 (m, 2 H) 7.31-7.35 (m, 2 H) 7.43 (t, J=7.6 Hz, 2H) 7.52-7.58 (m, 4 H).

後処理

  1. temperatureThe reaction mixture is cooled to room temperature
  2. customquenched with brine
  3. extractionThe mixture is extracted twice with ethylacetate
  4. washthe combined 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 silica gel flash column chromatography (heptane/EtOAc=100:0 to 50:50)

出典と根拠

ORDレコード
ord-a28081fcba2641639581f13282e7a4c4
出典データセット
uspto-grants-2014_09
特許番号
US08822534B2

関連ノート

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