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

HRID 1945060

反応式

HRID 1945060 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.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.[Cl-].[Na+].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: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:30]=[C:25]([Cl:24])[CH:26]=[CH:27][C:28]=2[Cl:31])=[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

7

反応物 3

HCID 10340Sodium CarbonateHCID 27733712,5-Dichlorobenzeneboronic acidHCID 59607624(R)-Ethyl 4-(4-bromophenyl)-3-((tert-butoxycarbonyl)amino)butanoate

生成物 1

HCID 59607666(R)-ethyl 3-(tert-butoxycarbonylamino)-4-(2',5'-dichlorobiphenyl-4-yl)butanoate収率 92.7%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒HCID 57417360Sodium chloride; water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 (1.005 g, 2.60 mmol), 2,5-dichlorophenylboronic acid (0.745 g, 3.90 mmol), Pd(PPh3)4 (0.301 g, 0.260 mmol) and 2 M aqueous Na2CO3 (2.60 ml, 5.20 mmol) in 1,2-dimethoxyethane (20 ml) is allowed to stir at 95° C. under nitrogen for 3 hours. The reaction mixture is cooled to room temperature and diluted with brine. The two phases are separated. The products are extracted twice with ethyl acetate (2×100 ml) 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-(2′,5′-dichlorobiphenyl-4-yl)butanoate (1.09 g); HPLC retention time=1.50 minutes (condition B); MS (ES+)=352.00 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.28 (t, J=7.1 Hz, 3H) 1.41 (s, 9H) 2.45-2.58 (m, 2H) 2.85-3.00 (m, 2H) 4.17 (t, J=7.1 Hz, 2H) 4.20 (br s, 1H) 5.06-5.08 (m, 1H) 7.23-7.28 (m, 3H) 7.31-7.40 (m, 4H).

後処理

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

出典と根拠

ORDレコード
ord-1dc834da74de41f581176af7c702f274
出典データセット
uspto-grants-2013_03
特許番号
US08394853B2

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