Sodium Carbonate → HCID 131719174, compound

HRID 2211390Notes

Reaction equation

HRID 2211390 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 2.0M 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. De-benzylation and hydrolysis proceeded as described above for the preparation of Example 60. Salt formation and purification as described above for the preparation of Example 59(D) provided 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. Analysis for C33H31O6F2Na.H2O: Calc: C, 65.77; H, 5.52; Found: C, 65.81; H, 5.41.

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. customDe-benzylation and hydrolysis
  8. customas described above for the preparation of Example 60
  9. customSalt formation and purification
  10. customas described above for the preparation of Example 59(D)

Sources & evidence

ORD record
ord-59a14af104954612ba10c5a5d81df03f
Source dataset
uspto-grants-1995_10
Patent number
US05462954

Reaction notes

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