Triphenylphosphine → 5-{3-(3-(3-Hydroxy-2-methoxycarbonyl-phenoxy)-propyl)-phenyl}-isoxazole-3-carboxylic Acid

HRID 1375666Notes

Reaction equation

HRID 1375666 reaction equation
C([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][CH2:18][CH2:19][OH:20])[CH:12]=2)[O:8][N:7]=1)=[O:5])C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:40][C:41]1[CH:50]=[CH:49][CH:48]=[C:47](O)[C:42]=1[C:43]([O:45][CH3:46])=[O:44].CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[OH:40][C:41]1[C:42]([C:43]([O:45][CH3:46])=[O:44])=[C:47]([CH:48]=[CH:49][CH:50]=1)[O:20][CH2:19][CH2:18][CH2:17][C:13]1[CH:12]=[C:11]([C:9]2[O:8][N:7]=[C:6]([C:4]([OH:3])=[O:5])[CH:10]=2)[CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 519869Methyl 2,6-dihydroxybenzoateHCID 5462977Diethyl azodicarboxylateHCID 695081845-(3-(3-Hydroxy-propyl)-phenyl)-isoxazole-3-carboxylic Acid Ethyl Ester

Product 1

HCID 100463425-{3-(3-(3-Hydroxy-2-methoxycarbonyl-phenoxy)-propyl)-phenyl}-isoxazole-3-carboxylic AcidYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 5-(3-(3-hydroxy-propyl)-phenyl)-isoxazole-3-carboxylic acid ethyl ester (31 mg, 0.1 mmol) was added triphenylphosphine (29 mg, 0.11 mmol), methyl (2,6-dihydroxy)benzoate (20 mg, 0.12 mmol), then THF (1 mL). After the solids had dissolved, diethylazodicarboxylate (20 μL, 0.13 mmol) was added, and the reaction was stirred at ambient temperature for 1 hour. The reaction was concentrated in vacuo, and the residue was taken up in aqueous 2M NaOH (1 mL), along with enough methanol to make the solution homogeneous. After stirring for 10 minutes, the solvents were removed in vacuo, glacial acetic acid (4 drops)was added, and the product was purified by reverse phase HPLC, eluting with a acetonitrile/0.1% aq. trifluoroacetic acid gradient to provide the title compound (2.7 mg, 7%). 1H NMR (500 MHz, d6-DMSO) δ 9.94 (s, 1H), 7.79 (s, 1H), 7.76 (d, 1H, J=7.8 Hz), 7.46 (t, 1H, J=7.6 Hz), 7.37 (d, 1H, J=7.5 Hz), 7.34 (s, 1H), 7.15 (t, 1H, J=8.3 Hz), 6.49 (dd, 2H, J=2.8, 8.4 Hz), 3.95 (t, 2H, J=6.2 Hz), 3.79 (s, 3H), 2.78 (t, 2H, J=7.5 Hz), 2.01 (m, 2H); MS (ESI) m/z 398 (M+H), 415 (M+NH4).

Workup

  1. dissolutionAfter the solids had dissolved
  2. concentrationThe reaction was concentrated in vacuo
  3. stirringAfter stirring for 10 minutes
  4. customthe solvents were removed in vacuo, glacial acetic acid (4 drops)
  5. additionwas added
  6. customthe product was purified by reverse phase HPLC
  7. washeluting with a acetonitrile/0.1% aq. trifluoroacetic acid gradient

Sources & evidence

ORD record
ord-e5de3e5c7dff419e88fba206cb834224
Source dataset
uspto-grants-2007_01
Patent number
US07169797B2

Reaction notes

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