(3-Chlorophenyl)boronic acid → (R)-benzyl 3-(tert-butoxycarbonylamino)-4-(3'-chlorobiphenyl-4-yl)butanoate

HRID 70881노트

반응식

HRID 70881 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:10][C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])=[CH:4][CH:3]=1.[Cl:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1>C1(C)C=CC=CC=1.[Cl-].[Na+].O.CCOC(C)=O.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:25]([O:24][C:22]([NH:21][C@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:34]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:29])[CH:35]=2)=[CH:3][CH:4]=1)[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:23])([CH3:28])([CH3:27])[CH3:26]

참가 물질

7

반응물 2

HCID 2734323(3-Chlorophenyl)boronic acidHCID 59607538(R)-benzyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate

생성물 1

HCID 59607651(R)-benzyl 3-(tert-butoxycarbonylamino)-4-(3'-chlorobiphenyl-4-yl)butanoate수율 48.1%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
95 °C

실험 절차

A suspension of give (R)-benzyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (2.00 g, 4.46 mmol), 3-chlorophenylboronic acid (1.046 g, 6.69 mmol), Pd(PPh3)4 (0.515 g, 0.446 mmol) and Na2CO3aq (4.46 ml, 8.92 mmol) in Toluene (30 ml) is allowed to stir under nitrogen at 95° C. for 19 hr. The reaction mixture is cooled to ambient temperature, and diluted with brine and EtOAc. The products are extracted twice with EtOAc, washed with brine, dried over MgSO4, filtered, and concentrated. The residue is purified by flash column chromatography on 90 g silica gel (eluent: heptane/EtOAc=100:0 to 65:35) to give (R)-benzyl 3-(tert-butoxycarbonylamino)-4-(3′-chlorobiphenyl-4-yl)butanoate (1.03 g); HPLC retention time=1.74 minutes (condition B); MS (ES+)=380.2 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 9 H) 2.52 (A of ABX, Jab=15.9 Hz, Jax=5.8 Hz, 1 H) 2.58 (B of ABX, Jab=15.9 Hz, Jbx=5.6 Hz, 1 H) 2.81-2.98 (m, 2 H) 4.19 (br s, 1 H) 5.07 (br d, 1 H) 5.12 (A of AB, J=12.3 Hz, 1 H) 5.17 (A of AB, J=12.3 Hz, 1 H) 7.20-7.22 (m, 2 H) 7.28-7.39 (m, 7 H) 7.42-7.47 (m, 3 H) 7.53-7.54 (m, 1 H).

후처리

  1. temperatureThe reaction mixture is cooled to ambient temperature
  2. extractionThe products are extracted twice with EtOAc
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by flash column chromatography on 90 g silica gel (eluent: heptane/EtOAc=100:0 to 65:35)

출처 및 근거

ORD 기록
ord-d91ae9bb0dcd4cb2998c0393a98af510
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822534B2

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