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

HRID 881860

반응식

HRID 881860 반응식
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.[Cl:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[C:20]([O:19][C:17]([NH:16][C@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:29]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:24])[CH:30]=2)=[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]

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 59607624(R)-Ethyl 4-(4-bromophenyl)-3-((tert-butoxycarbonyl)amino)butanoate

생성물 1

HCID 59607603(R)-ethyl 3-(tert-butoxycarbonylamino)-4-(3'-chlorobiphenyl-4-yl)butanoate수율 62.9%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
95 °C

실험 절차

A mixture of (R)-ethyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (4.89 g, 12.66 mmol), 3-chlorophenylboronic acid (2.97 g, 18.99 mmol), Pd(PPh3)4 (1.463 g, 1.266 mmol) and 2 M aqueous Na2CO3 (12.66 ml, 25.3 mmol) in 1,2-dimethoxyethane (100 ml) is allowed to stir at 95° C. under nitrogen for 3 hours. The reaction mixture is cooled to room temperature and quenched with brine. The two phases are separated. The mixture is extracted twice with ethyl acetate from the aqueous layer. The combined organic layer is washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30) to give (R)-ethyl 3-(tert-butoxycarbonylamino)-4-(3′-chlorobiphenyl-4-yl)butanoate (3.33 g); HPLC retention time=1.44 minutes (condition B); MS (ES+)=318.26 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.28 (t, J=7.2 Hz, 3 H) 1.41 (s, 9 H) 2.47 (A of ABX, Jab=15.8 Hz, Jax=5.9 Hz, 1 H) 2.52 (B of ABX, Jab=15.8 Hz, Jbx=5.4 Hz, 1 H) 2.83-2.89 (m, 1 H) 2.95-3.00 (m, 1 H) 4.17 (q, J=7.2 Hz, 2 H) 4.18 (br s, 1 H) 5.07 (br s, 1 H) 7.26-7.37 (m, 4 H) 7.43-7.51 (m, 3 H) 7.55 (br t, J=1.8 Hz, 1 H).

후처리

  1. temperatureThe reaction mixture is cooled to room temperature
  2. customquenched with brine
  3. customThe two phases are separated
  4. extractionThe mixture is extracted twice with ethyl acetate from the aqueous layer
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30)

출처 및 근거

ORD 기록
ord-8ccd0dabc95d490d802d9327432a1f63
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993631B2

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