Sodium Carbonate → HCID 59607779, compound

HRID 70888

Reaction equation

HRID 70888 reaction equation
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.[F:24][C:25]1[CH:26]=[CH:27][C:28]([O:34][CH3:35])=[C:29](B(O)O)[CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=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:27]2[CH:26]=[C:25]([F:24])[CH:30]=[CH:29][C:28]=2[O:34][CH3:35])=[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]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 59607624(R)-Ethyl 4-(4-bromophenyl)-3-((tert-butoxycarbonyl)amino)butanoate

Product 1

HCID 59607779HCID 59607779, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of (R)-ethyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate, (3.12 g, 8.08 mmol), and 5-fluoro-2-methoxyphenylboronic acid (2.2 g, 12.93 mmol) in toluene (52 mL) and is added PdCl2(dppf)CH2Cl2 adduct (0.66 g, 0.81 mmol) and 2M aq. Na2CO3 (8.1 mL, 16.16 mmol). After stirring at 95° C. under nitrogen for 4 hours, the solution is cooled to ambient temperature and then quenched with ice water. 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 50:50) to give (R)-ethyl 3-(tert-butoxycarbonylamino)-4-(5′-fluoro-2′-methoxybiphenyl-4-yl)butanoate (2.86 g). HPLC retention time=1.80 minutes (condition A); MS (m+1)=432.2; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (t, J=7.1 Hz, 3 H) 1.45 (s, 9 H) 2.45-2.65 (m, 2 H) 2.83-2.94 (m, 1 H) 2.94-3.09 (m, 1 H) 3.80 (s, 3 H) 4.20 (q, J=7.2 Hz, 2 H) 4.24-4.33 (m, 1 H) 5.11 (br. s., 1 H) 6.90-6.96 (m, 1 H) 7.00 (dd, J=7.8, 3.3 Hz, 1 H) 7.06 (dd, J=9.2, 3.2 Hz, 1 H) 7.27 (d, J=7.8 Hz, 2 H) 7.49 (d, J=7.8 Hz, 2 H)

Workup

  1. temperaturethe solution is cooled to ambient temperature
  2. customquenched with ice water
  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 50:50)

Sources & evidence

ORD record
ord-77c31c2646ba4dd28132a8f7d5bd1789
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Linked notes

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