Acetic Acid → HCID 67170951, compound

HRID 1506546Notes

Reaction equation

HRID 1506546 reaction equation
OC([C:5]1[CH:6]=[C:7]2[C:24](=[CH:25][CH:26]=1)[C:11]1=[N:12][O:13][C:14]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH3:23])=[CH:17][CH:16]=3)=[C:10]1[CH2:9][CH2:8]2)C#N.Cl.[OH2:28].[CH3:29][C:30]([OH:32])=[O:31]>>[OH:28][CH:29]([C:5]1[CH:6]=[C:7]2[C:24](=[CH:25][CH:26]=1)[C:11]1=[N:12][O:13][C:14]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH3:23])=[CH:17][CH:16]=3)=[C:10]1[CH2:9][CH2:8]2)[C:30]([OH:32])=[O:31]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 962WaterHCID 86669938HCID 86669938, compound

Product 1

HCID 67170951HCID 67170951, compoundYield 13%

Conditions

Temperature
70 °C

Procedure

To a solution of 2-hydroxy-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetonitrile (Preparation 127A, 120 mg, 0.35 mmol) in glacial AcOH (1.5 mL) was added concentrated HCl (0.5 mL). The reaction mixture was stirred at 70° C. for 8 h. After cooling, the solution was poured into water and was extracted with ethyl acetate. The organic layer was dried (over magnesium sulfate), filtered, and concentrated. The resulting residue was purified by preparative HPLC (Phenomenex Luna 5 u C18 21.2×100 mm, Solvent A: 90% water with 10% MeOH and 0.1% TFA, Solvent B: 90% MeOH with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention time=12.1 min) to give 2-hydroxy-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetic acid (20 mg, 0.049 mmol, 13% yield): product HPLC ret. time=9.59 min. (condition G); LC/MS M+1=364.1; 1H NMR (400 MHz, CD3OD) δ ppm 7.87 (1H, d, J=7.92 Hz), 7.70 (2H, d, J=8.14 Hz), 7.41-7.57 (2H, m), 7.35 (2H, d, J=8.14 Hz), 5.19 (1H, s), 3.04 (4H, s), 2.66 (2H, t, J=7.59 Hz), 1.60-1.77 (2H, m), 0.97 (3H, t, J=7.26 Hz).

Workup

  1. temperatureAfter cooling
  2. extractionwas extracted with ethyl acetate
  3. dry with materialThe organic layer was dried (over magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by preparative HPLC (Phenomenex Luna 5 u C18 21.2×100 mm, Solvent A: 90% water with 10% MeOH and 0.1% TFA, Solvent B: 90% MeOH with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention time=12.1 min)

Sources & evidence

ORD record
ord-1fb2b0c2e59b4831b07422da8d78c0b5
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

Loading…