Toluene → 2-Butoxycarbonylamino-3-(4'-dibenzofuran-4-yl-biphen-4-ylmethylsulfanyl)-3,3-dimethylpropanoic acid methyl ester

HRID 900380Notes

Reaction equation

HRID 900380 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH:4]([NH:17][C:18]([O:20][C:21]([CH3:24])(C)C)=[O:19])[C:5]([S:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13](Br)=[CH:12][CH:11]=1)([CH3:7])[CH3:6].[CH:26]1[C:34]2[C:33]3[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=3[O:31][C:30]=2[C:29]([C:39]2[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=2)=[CH:28][CH:27]=1.C([O-])([O-])=O.[K+].[K+].[C:54]1(C)C=CC=C[CH:55]=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:25])[CH:4]([NH:17][C:18]([O:20][CH2:21][CH2:24][CH2:54][CH3:55])=[O:19])[C:5]([S:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]([C:42]2[CH:43]=[CH:44][C:39]([C:29]3[C:30]4[O:31][C:32]5[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=5[C:34]=4[CH:26]=[CH:27][CH:28]=3)=[CH:40][CH:41]=2)=[CH:14][CH:15]=1)([CH3:6])[CH3:7]

Participants

8

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 59655966(4-(Dibenzo[b,d]furan-4-yl)phenyl)boronic acidHCID 596962022-Tert-butoxycarbonylamino-3-(4-bromophenylmethylsulfanyl)-3,3-dimethylpropanoic acid methyl ester

Product 1

HCID 1317268292-Butoxycarbonylamino-3-(4'-dibenzofuran-4-yl-biphen-4-ylmethylsulfanyl)-3,3-dimethylpropanoic acid methyl esterYield 72%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-tert-butoxycarbonylamino-3-(4-bromophenylmethylsulfanyl)-3,3-dimethylpropanoic acid methyl ester (0.432 g, 1 mmol), 4-(4-dibenzofuranyl)benzeneboronic acid (0.305 g, 1.05 mmol) and Pd(PPh3)4 (0.052 g, 5 mol %) in toluene (10 mL) and ethanol (3.0 mL) was treated with 2 M K2CO3 (1.5 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 the desired product (430 mg, 72%) as an oil. 1H NMR (CDCl3), δ 8.01 (d, J=8 Hz, 2H), 7.94 (d, J=8 Hz, 2H), 7.78 (d, J=8 Hz, 2H), 7.66 (m, 4H), 7.42 (m, 5H), 5.44 (d, J=9 Hz, 1H), 4.46 (d, J=9 Hz, 1H), 3.87 (s, 2H), 3.81 (s, 3H), 1.44 (s, 9H). LCMS 618 (M++23).

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-76d1d40cd4cf40aaaf9baaf7a60ab025
Source dataset
uspto-grants-2008_04
Patent number
US07358248B2

Reaction notes

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