Toluene → HCID 67103012, compound

HRID 2079853Notes

Reaction equation

HRID 2079853 reaction equation
[CH2:1]([O:8][C:9]1[CH:22]=[C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:20](Br)=[CH:19][C:10]=1[C:11]([NH:13][CH2:14][CH2:15][CH2:16][O:17][CH3:18])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:32]([C:35]1[CH:36]=[CH:37][C:38]([O:44][CH3:45])=[C:39](B(O)O)[CH:40]=1)([CH3:34])[CH3:33].C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+]>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(O)C>[CH3:18][O:17][CH2:16][CH2:15][CH2:14][NH:13][C:11]([C:10]1[CH:19]=[C:20]([C:39]2[CH:40]=[C:35]([CH:32]([CH3:34])[CH3:33])[CH:36]=[CH:37][C:38]=2[O:44][CH3:45])[C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:22][C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:12]

Participants

7

Reactant 4

HCID 1140TolueneHCID 516892Sodium BicarbonateHCID 45891905-Isopropyl-2-methoxyphenylboronic acidHCID 57695546HCID 57695546, compound

Product 1

HCID 67103012HCID 67103012, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Procedure

The mixture of 2,4-bis-benzyloxy-5-bromo-N-(3-methoxy-propyl)-benzamide (484 mg, 1 mmol) and 5-isopropyl-2-methoxy-phenylboronic acid (388 mg, 2 mmol) was heated in the mixture of toluene (5 ml), ethanol (5 ml) and saturated NaHCO3 (5 ml) under nitrogen in the presence of a catalytic amount of Pd(PPh3)4 (60 mg, 0.056 mmol) at 80° C. for 2-3 h. After the reaction was complete, the reaction mixture was extracted with ethyl acetate (25 ml×3), and the combined organics were washed with water and brine and dried over Na2SO4. After filtration and concentration, the residue was purified by flash chromatography on silica gel to provide 508 mg of 4,6-bis-benzyloxy-5′-isopropyl-2′-methoxy-biphenyl-3-carboxylic acid-(3-methoxypropyl)-amide (92% yield). M.p.: 142-144 C; 400 MHz 1H NMR (CDCl3) δ: 8.16 (s, 1H), 7.92 (t, J=5.6 Hz, 1H), 7.43-7.38 (m, 5H), 7.33-7.26 (m, 5H), 7.17 (dd, J=8.4, 2.4 Hz, 1H), 7.12 (d, J=1.6 Hz, 1H), 6.87 (d, J=8.0 Hz, 1H), 6.59 (s, 1H), 5.11 (s, 2H), 5.06 (s, 2H), 3.72 (s, 3H), 3.44 (q, J=5.6 Hz, 2H), 3.30 (t, J=6.4 Hz, 2H), 3.22 (s, 3H), 2.87 (m, 1H), 1.69 (pent, J=6.4 Hz, 2H), 1.23 (d, J=6.8 Hz, 6H); LCMS: 554 [M+H].

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate (25 ml×3)
  2. washthe combined organics were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationAfter filtration and concentration
  5. customthe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-fb13284420ec4398a10401f3db13ea04
Source dataset
uspto-grants-2011_04
Patent number
US07932279B2

Reaction notes

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