Hydrochloric Acid → HCID 53234306, compound

HRID 1506339Notes

Reaction equation

HRID 1506339 reaction equation
[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][N:13]=[C:12]3[C:15]4[C:20]([CH2:21][CH2:22][C:11]=23)=[CH:19][C:18]([OH:23])=[CH:17][CH:16]=4)=[CH:6][CH:5]=1)[CH2:2][CH3:3].C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S([O:40][CH2:41][C@H:42]2[CH2:46]OC(C)(C)[O:43]2)(=O)=O)=CC=1.Cl>C(#N)C.C(O)C.CO>[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][N:13]=[C:12]3[C:15]4[C:20]([CH2:21][CH2:22][C:11]=23)=[CH:19][C:18]([O:23][CH2:46][C@H:42]([OH:43])[CH2:41][OH:40])=[CH:17][CH:16]=4)=[CH:6][CH:5]=1)[CH2:2][CH3:3]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 6993835(R)-(-)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-Toluenesulfonate2×HCID 136065803HCID 136065803, compound

Product 1

HCID 53234306HCID 53234306, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-ol (Example 9, 0.1 g, 0.327 mmol) in acetonitrile (2 mL) was added potassium carbonate (0.100 g, 0.720 mmol) and (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (0.094 g, 0.327 mmol) at room temperature. The heterogeneous reaction mixture was heated at 120° C. in a microwave reactor for 1 h. Next, 2 mL of methanol was added followed by additional (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (100 mg). The contents were heated in the microwave reactor at 120° C. for 1 h. To the reaction mixture was added 1.0 mL of 2.5 M hydrochloric acid in ethanol at room temperature. The heterogeneous reaction mixture was stirred at room temperature for 1.5 h and concentrated under reduced pressure. Methanol (3 mL) was added followed by 3 drops of water and the contents were filtered. The pale yellow filtrate was subjected to Prep. HPLC (PHENOMENEX® Luna Axia 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA). Fractions corresponding to the desired product were isolated and concentrated to yield (R)-3-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yloxy)propane-1,2-diol (0.016 g, 0.042 mmol, 13% yield) as a white solid. The compound had an HPLC retention time=3.73 min (condition C); LC/MS M+1=380.1; 1H NMR (400 MHz, CDCl3) δ ppm 7.93 (d, J=8.53 Hz, 1H) 7.69 (d, J=8.28 Hz, 2H) 7.31 (d, J=8.28 Hz, 2H) 6.85-6.92 (m, 2H) 4.08-4.15 (m, 3H) 3.74-3.91 (m, 2H) 2.96-3.05 (m, 4H) 2.55-2.68 (m, 3H) 1.97 (t, J=5.90 Hz, 1H) 1.68 (sxt, J=7.43 Hz, 2H) 0.97 (t, 3H).

Workup

  1. temperatureThe contents were heated in the microwave reactor at 120° C. for 1 h
  2. concentrationconcentrated under reduced pressure
  3. additionMethanol (3 mL) was added
  4. filtrationthe contents were filtered
  5. customHPLC (PHENOMENEX® Luna Axia 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA)

Sources & evidence

ORD record
ord-89e65a516f9e4e7ca30aed7d5b63361c
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

Loading…