(4-Methoxyphenyl)boronic acid → HCID 131727745, compound

HRID 473532Notes

Reaction equation

HRID 473532 reaction equation
[CH2:1]([O:48][CH:49]1[C@H:53]2[C@H:54]([O:74][Si:75]([C:78]([CH3:81])([CH3:80])[CH3:79])([CH3:77])[CH3:76])[N:55]([C:66]([O:68][CH2:69][C:70]([Cl:73])([Cl:72])[Cl:71])=[O:67])[C:56]3[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][C:57]=3[C:58](=[O:59])[N:52]2[CH:51]=[C:50]1OS(C(F)(F)F)(=O)=O)[CH2:2][CH2:3][CH2:4][CH2:5][O:6][CH:7]1[C@H:11]2[C@H:12]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[N:13]([C:24]([O:26][CH2:27][C:28]([Cl:31])([Cl:30])[Cl:29])=[O:25])[C:14]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:15]=3[C:16](=[O:17])[N:10]2[CH:9]=[C:8]1OS(C(F)(F)F)(=O)=O.[CH3:90][O:91][C:92]1[CH:97]=[CH:96][C:95](B(O)O)=[CH:94][CH:93]=1.C[CH2:102][O:103][C:104]([CH3:106])=O.[CH3:107][CH2:108][CH2:109][CH2:110]CC>O.CCO.C1(C)C=CC=CC=1.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>[CH2:5]([O:6][CH:7]1[C@H:11]2[C@H:12]([O:32][Si:33]([C:36]([CH3:39])([CH3:37])[CH3:38])([CH3:35])[CH3:34])[N:13]([C:24]([O:26][CH2:27][C:28]([Cl:31])([Cl:30])[Cl:29])=[O:25])[C:14]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:15]=3[C:16](=[O:17])[N:10]2[CH:9]=[C:8]1[C:108]1[CH:107]=[CH:106][C:104]([O:103][CH3:102])=[CH:110][CH:109]=1)[CH2:4][CH2:3][CH2:2][CH2:1][O:48][CH:49]1[C@H:53]2[C@H:54]([O:74][Si:75]([C:78]([CH3:81])([CH3:80])[CH3:79])([CH3:76])[CH3:77])[N:55]([C:66]([O:68][CH2:69][C:70]([Cl:71])([Cl:72])[Cl:73])=[O:67])[C:56]3[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][C:57]=3[C:58](=[O:59])[N:52]2[CH:51]=[C:50]1[C:95]1[CH:96]=[CH:97][C:92]([O:91][CH3:90])=[CH:93][CH:94]=1

Participants

8

Reactant 3

HCID 201262(4-Methoxyphenyl)boronic acidHCID 21226206Ethyl acetate hexaneHCID 131727746HCID 131727746, compound

Product 1

HCID 131727745HCID 131727745, compoundYield 52%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Pd(PPh3)4 (7.43 mg, 6.43 μmol) was added to a solution of the triflate 44 (236 mg, 0.16 mmol), 4-methoxyphenylboronic acid (63 mg, 0.42 mmol), TEA (0.13 mL, 98 mg, 0.97 mmol) in H2O (0.8 mL), EtOH (5 mL) and toluene (5 mL) at room temperature. The reaction mixture was heated in the microwave at 100° C. for 30 minutes after which time TLC (80:20 v/v EtOAc/hexane) revealed the complete consumption of the starting material. Excess solvent was removed by evaporation in vacuo and the resulting residue was dissolved in EtOAc (50 mL), washed with H2O (20 mL), brine (20 mL) and dried (MgSO4). Filtration and evaporation of solvent afforded the crude product which was purified by flash column chromatography (gradient elution: 80:20 v/v Hexane/EtOAc to 50:50 v/v Hexane/EtOAc) to afford C2-aryl product 45 as a yellow glass (117 mg, 52%): 1H NMR (400 MHz, CDCl3) δ 7.35 (s, 2H), 7.31 (s, 2H), 7.31-7.27 (m, 6H), 6.90 (d, 4H, J=8.8 Hz), 6.76 (s, 2H), 5.92 (d, 2H, J=8.8 Hz), 5.23 (d, 2H, J=12.0 Hz), 4.20 (d, 2H, J=12.1 Hz), 4.14-4.05 (m, 4H), 4.04-3.95 (m, 2H), 3.93 (s, 6H), 3.83 (s, 6H), 3.34 (ddd, 2H, J=16.3, 10.4, 2.0 Hz), 2.86-2.75 (m, 2H), 2.02-1.94 (m, 4H), 1.72-1.66 (m, 2H), 0.93 and 0.86 (s×2, 18H), 0.28 and 0.25 (s×2, 12H); 13C NMR (100 MHz, CDCl3) δ 163.7, 159.1, 153.7, 150.8, 149.3, 127.8, 126.3, 126.1, 125.4, 122.3, 122.2, 114.3, 114.2, 110.9, 95.3, 87.3, 74.8, 68.8, 61.5, 56.2, 55.4, 35.3, 28.8, 25.7, 22.8, 17.9, −4.0 and −5.1.

Workup

  1. customthe complete consumption of the starting material
  2. customExcess solvent was removed by evaporation in vacuo
  3. dissolutionthe resulting residue was dissolved in EtOAc (50 mL)
  4. washwashed with H2O (20 mL), brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationFiltration and evaporation of solvent
  7. customafforded the crude product which
  8. customwas purified by flash column chromatography (gradient elution: 80:20 v/v Hexane/EtOAc to 50:50 v/v Hexane/EtOAc)

Sources & evidence

ORD record
ord-11fe325455584c48bc3f7337c901b7eb
Source dataset
uspto-grants-2014_01
Patent number
US08633185B2

Reaction notes

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