Potassium Carbonate → 2-tert-Butoxycarbonylamino-3-(4'-dibenzofuran-4-yl-biphen-4-yl)-propanoic acid methyl ester

HRID 1782671Notes

Reaction equation

HRID 1782671 reaction equation
[CH3:1][O:2][C:3](=[O:21])[CH:4]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9](I)=[CH:8][CH:7]=1.[CH:22]1[C:30]2[C:29]3[CH:31]=[CH:32][CH:33]=[CH:34][C:28]=3[O:27][C:26]=2[C:25]([C:35]2[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=2)=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C(OCC)(=O)C.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>[CH3:1][O:2][C:3](=[O:21])[CH:4]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:38]2[CH:39]=[CH:40][C:35]([C:25]3[C:26]4[O:27][C:28]5[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=5[C:30]=4[CH:22]=[CH:23][CH:24]=3)=[CH:36][CH:37]=2)=[CH:8][CH:7]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 13875796(+-)-(R/S)-2-tert-Butoxycarbonylamino-3-(4-iodo-phenyl)-propionic acid methyl esterHCID 59655966(4-(Dibenzo[b,d]furan-4-yl)phenyl)boronic acid

Product 1

HCID 1317268262-tert-Butoxycarbonylamino-3-(4'-dibenzofuran-4-yl-biphen-4-yl)-propanoic acid methyl esterYield 70.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-tert-Butoxycarbonylamino-3-(4-iodophenyl)-propanoic acid methyl ester (1.22 g, 3 mmol), 4-(4-dibenzofuranyl)benzeneboronic acid (0.906 g, 3.15 mmol) and Pd(PPh3)4 (160 mg, 5 mol %) in toluene (25 mL) and ethanol (6.0 mL) was treated with 2 M K2CO3 (4.5 mL). The reaction mixture was heated to reflux for 2 h, cooled to room temperature, diluted with ethyl acetate (100 mL). The organic layer was washed successively with 2% aq HCl and sat. aq NaCl, dried over MgSO4 and concentrated. Purification by flash column chromatography (2-10% ethyl acetate in heptane) gave 2-tert-Butoxycarbonylamino-3-(4′-dibenzofuran-4-yl-biphen-4-yl)-propanoic acid methyl ester (1.1 g, 70%) as an oil. 1H NMR (CDCl3), δ 7.98 (d, J=9 Hz, 2 H), 7.96 (d, J=8 Hz, 2 H), 7.74 (d, J=9, 2H), 7.66 (m, 4 H), 7.42 (m, 5 H), 5.04 (d, J=9 Hz, 1 H), 4.66 (m, 1 H), 3.73 (s, 3 H), 3.15 (m, 2 H), 1.57 (s, 9 H). LCMS 422 (M+−100).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 h
  3. washThe organic layer was washed successively with 2% aq HCl and sat. aq NaCl
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification by flash column chromatography (2-10% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-c1e6650e50484852b3b264bedba24929
Source dataset
uspto-grants-2009_03
Patent number
US07498356B2

Reaction notes

Loading…