Hydrochloric Acid → N-{1-[[5-methyl-3-(2-methylsulfonylphenylsulfonyloxy)phenoxy]methyl]cyclopropylmethoxy}amine

HRID 1977953Notes

Reaction equation

HRID 1977953 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([O:26][S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[S:36]([CH3:39])(=[O:38])=[O:37])(=[O:29])=[O:28])[CH:5]=[C:6]([CH:25]=1)[O:7][CH2:8][C:9]1([CH2:12][O:13][N:14]2C(=O)C3=CC=CC=C3C2=O)[CH2:11][CH2:10]1.O1CCCC1.[BH4-].[Na+].Cl>C(O)C.O>[CH3:1][C:2]1[CH:3]=[C:4]([O:26][S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[S:36]([CH3:39])(=[O:38])=[O:37])(=[O:29])=[O:28])[CH:5]=[C:6]([CH:25]=1)[O:7][CH2:8][C:9]1([CH2:12][O:13][NH2:14])[CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 22722590n-{1-[[5-Methyl-3-(2-methylsulfonylphenylsulfonyloxy)phenoxy]methyl]cyclopropylmethoxy}phthalimide

Product 1

HCID 22722412N-{1-[[5-methyl-3-(2-methylsulfonylphenylsulfonyloxy)phenoxy]methyl]cyclopropylmethoxy}amineYield 86%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of N-{1-[[5-methyl-3-(2-methylsulfonylphenylsulfonyloxy)phenoxy]methyl]cyclopropylmethoxy}phthalimide (5.4 g, 9.5 mmol), as prepared in the preceding step, in ethanol (100 mL)/tetrahydrofuran (100 mL)/water (50 mL) was added sodium borohydride (1.15 g, 30.0 mmol). The reaction mixture was stirred at ambient temperature overnight. 2N HCl was added to adjust the pH to 1-2, the mixture was heated to 50° C. for 2 hours. The reaction mixture was concentrated to about 100 mL, water (50 mL) was added and the mixture was neutralized to pH 8-9 with 2N NaOH. The mixture was extracted into ethyl acetate (3×100 mL) and the organic phase was washed with brine (2×100 mL) and then dried over Na2SO4. After removing the solvent, the residue was purified by flash column chromatography (4:1 ethyl acetate/hexane) to give the title compound as a white solid (3.6 g, 86%). 1H-NMR (300 MHz, CDCl3) δ8.45 (d, J=7.8 Hz, 1H), 8.13 (d, J=7.8 Hz, 1H), 7.88 (t, J=7.7 Hz, 1H), 7.74 (t, J=7.7 Hz, 1H), 6.61 (s, 1H), 6.58 (s, 2H), 5.44 (br s, 2H),3.76 (s, 2H), 3,63 (s 2H), 3.45 (s, 3H), 2.23 (s, 3H), 0.57-0.65 (m, 4H).

Workup

  1. temperaturethe mixture was heated to 50° C. for 2 hours
  2. concentrationThe reaction mixture was concentrated to about 100 mL, water (50 mL)
  3. additionwas added
  4. extractionThe mixture was extracted into ethyl acetate (3×100 mL)
  5. washthe organic phase was washed with brine (2×100 mL)
  6. dry with materialdried over Na2SO4
  7. customAfter removing the solvent
  8. customthe residue was purified by flash column chromatography (4:1 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e62dfdde0a6840d2aec1b97f7ffa999d
Source dataset
uspto-grants-2001_05
Patent number
US06235778B1

Reaction notes

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