Sodium Carbonate → HCID 131719174, compound

HRID 1977918Notes

Reaction equation

HRID 1977918 reaction equation
C[O:2][C:3](=[O:43])[C:4]1[C:9]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][O:21][C:22]3[CH:27]=[C:26]([O:28]CC4C=CC=CC=4)[C:25](Br)=[CH:24][C:23]=3[CH2:37][CH3:38])[C:12]=2[CH2:39][CH2:40][CH3:41])=[CH:8][CH:7]=[CH:6][C:5]=1[F:42].C(=O)([O-])[O-].[Na+:48].[Na+].[F:50][C:51]1[CH:56]=[CH:55][C:54](B(O)O)=[CH:53][CH:52]=1>C1C=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>[OH2:2].[Na+:48].[Na+:48].[F:42][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][O:21][C:22]3[CH:27]=[C:26]([OH:28])[C:25]([C:54]4[CH:55]=[CH:56][C:51]([F:50])=[CH:52][CH:53]=4)=[CH:24][C:23]=3[CH2:37][CH3:38])[C:12]=2[CH2:39][CH2:40][CH3:41])[C:4]=1[C:3]([O-:2])=[O:43].[F:42][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][O:21][C:22]3[CH:27]=[C:26]([OH:28])[C:25]([C:54]4[CH:55]=[CH:56][C:51]([F:50])=[CH:52][CH:53]=4)=[CH:24][C:23]=3[CH2:37][CH3:38])[C:12]=2[CH2:39][CH2:40][CH3:41])[C:4]=1[C:3]([O-:2])=[O:43]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 10580124HCID 10580124, compound

Product 1

HCID 131719174HCID 131719174, compoundYield 25%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-fluoro-6-[2-propyl-3-[3-[4-bromo-2-ethyl-5-(phenylmethoxy)phenoxy]propoxy]phenoxy]benzoic acid methyl ester (1.77 g, 2.72 mmol) in benzene (12 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.33 g, 0.30 mmol) and 2.0 M aqueous sodium carbonate (4 mL). To this mixture was added a solution of 4-fluorophenylboronic acid (4.10 g, 8.16 mmol) in ethanol (5 mL). The resulting mixture was refluxed for 4 hours then cooled to room temperature. The mixture was diluted with ethyl acetate and shaken. The organic layer was washed once with water and once with 1N aqueous sodium hydroxide, dried over sodium sulfate, filtered, and concentrated in vacuo to provide an oil. The product was de-benzylated, hydrolysed, salified, and purified to provide 403 mg (25%) of the desired title product as a fluffy white solid: NMR (DMSO-d6) 9.83 (bs, 1H), 7.50 (m, 2H), 6.96-7.16 (m, 4H), 6.96 (s, 1H), 6.74 (t, J=8.4 Hz, 2H), 6.57 (s, 1H), 6.40 (d, J =8.3 Hz, 1H), 6.35 (d, J=8.3 Hz, 1H), 4.16 (t, J=5.7 Hz, 2H), 4.05 (t, J=5.5 Hz, 2H), 2.40-2.58 (m, 4H), 2.18 (quintet, J=4.1 Hz, 2H), 1.41 (hextet, J=7.4 Hz, 2H), 1.07 (t, J=7.5 Hz, 3H), 0.80 (t, J=7.3 Hz, 3H); MS-FAB m/e 586 (p+1, 35), 585 (p, 100), 562 (33), 313 (30). IR (CHCl3, cm−1) 3300 (b), 2967, 1616, 1455, 1398, 1115.

Workup

  1. temperatureThe resulting mixture was refluxed for 4 hours
  2. washThe organic layer was washed once with water and once with 1N aqueous sodium hydroxide
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide an oil
  7. customhydrolysed, salified, and purified

Sources & evidence

ORD record
ord-82613e9540804b86876d72e9309dc054
Source dataset
uspto-grants-2001_05
Patent number
US06235785B1

Reaction notes

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