N-Hydroxyphthalimide → n-[3-[3-(5-Isoquinolinylsulfonyloxy)-5-methylphenoxy]propoxy]phthalimide

HRID 1977947Notes

Reaction equation

HRID 1977947 reaction equation
[CH:1]1[C:10]2[C:5](=[C:6]([S:11]([O:14][C:15]3[CH:16]=[C:17]([CH:23]=[C:24]([CH3:26])[CH:25]=3)[O:18][CH2:19][CH2:20][CH2:21][OH:22])(=[O:13])=[O:12])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[N:47]1[C:51](=[O:52])[C:50]2=[CH:53][CH:54]=[CH:55][CH:56]=[C:49]2[C:48]1=[O:57].N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.O>[CH:1]1[C:10]2[C:5](=[C:6]([S:11]([O:14][C:15]3[CH:16]=[C:17]([CH:23]=[C:24]([CH3:26])[CH:25]=3)[O:18][CH2:19][CH2:20][CH2:21][O:22][N:47]3[C:48](=[O:57])[C:49]4=[CH:56][CH:55]=[CH:54][CH:53]=[C:50]4[C:51]3=[O:52])(=[O:12])=[O:13])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

7

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 227225083-[3-(5-Isoquinolinylsulfonyloxy)-5-methylphenoxy]propanol

Product 1

HCID 22722554n-[3-[3-(5-Isoquinolinylsulfonyloxy)-5-methylphenoxy]propoxy]phthalimideYield 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[3-(5-isoquinolinylsulfonyloxy)-5-methylphenoxy]propanol (560 mg, 1.5 mmol), as prepared in the preceding step, triphenylphosphine (520 mg, 2.0 mmol), and N-hydroxyphthalimide (245 mg, 1.5 mmol) in tetrahydrofuran (15 mL) at 0° C. was added diethyl azodicarboxylate (350 mg, 2.0 mmol). The reaction mixture was stirred at room temperature overnight. Water (50 mL) was added, and the reaction mixture was extracted into ethyl acetate (3×50 mL). The ethyl acetate solution was washed with brine (2×50 mL) and dried over Na2SO4. After removing the solvent, the residue was purified by flash column chromatography (4:1 dichloromethane/ethyl acetate) to give the title compound as a colorless foam (580 mg, 75%). 1H-NMR (300 MHz, CDCl3) δ9.42 (s, 1H), 8.81 (d, J=6.1 Hz, 1H), 8.56 (d, J=6.1 Hz, 1H), 8.34 (d, J=7.1 Hz, 1H), 8.31 (d, J=7.2 Hz, 1H), 7.84 (m, 2H), 7.77 (m, 2H), 7.68 (t, J=7.7 Hz, 1H), 6.59 (s, 1H), 6.33 (s, 1H), 6.21 (s, 1H), 4.31 (t, J=6.1 Hz, 2H), 4.00 (t, J=6.1 Hz, 2H), 2.17 (s, 3H), 2.11 (m, 2H).

Workup

  1. extractionthe reaction mixture was extracted into ethyl acetate (3×50 mL)
  2. washThe ethyl acetate solution was washed with brine (2×50 mL)
  3. dry with materialdried over Na2SO4
  4. customAfter removing the solvent
  5. customthe residue was purified by flash column chromatography (4:1 dichloromethane/ethyl acetate)

Sources & evidence

ORD record
ord-070b1ac26e01497aa1c98dee7285642d
Source dataset
uspto-grants-2001_05
Patent number
US06235778B1

Reaction notes

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