Hydrochloric Acid → HCID 67170876, compound

HRID 1506551Notes

Reaction equation

HRID 1506551 reaction equation
OC([C:5]1[CH:6]=[C:7]2[C:30](=[CH:31][CH:32]=1)[C:11]1=[N:12][O:13][C:14]([C:15]3[C:19]([C:20]([F:23])([F:22])[F:21])=[C:18]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[O:17][N:16]=3)=[C:10]1[CH2:9][CH2:8]2)C#N.[OH2:33].Cl.[O:35]1[CH2:40][CH2:39][O:38]CC1>>[OH:35][CH:40]([C:5]1[CH:6]=[C:7]2[C:30](=[CH:31][CH:32]=1)[C:11]1=[N:12][O:13][C:14]([C:15]3[C:19]([C:20]([F:23])([F:22])[F:21])=[C:18]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[O:17][N:16]=3)=[C:10]1[CH2:9][CH2:8]2)[C:39]([OH:38])=[O:33]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 312751,4-DioxaneHCID 86669941HCID 86669941, compound

Product 1

HCID 67170876HCID 67170876, compound

Conditions

Temperature
100 °C

Procedure

To (±)-2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetonitrile (Preparation 131A, 1.1 g, 2.5 mmol) in dioxane (18.0 mL) was added water (12.0 mL) and hydrochloric acid, 37% (12 mL). The reaction mixture was heated at 100° C. for 3 h. After cooling, it was concentrated to provide the product as a racemic mixture. LC/MS M+1=458.0. The individual enantiomers were separated using a chiral preparative column under SFC conditions (Chiralcel OJ-H 5×25 cm, column temperature 20° C., isocratic elution with mobile phase 35% acetonitrile+0.1 TFA in CO2, 280 mL/min, 250 nM). Isomer 1 (500 mgs), retention time on chiral HPLC, 7.26 min; Isomer 2 (600 mgs), retention time on chiral HPLC, 9.88 min. The absolute stereochemistry at the carbon anchoring the secondary alcohol, of Isomer 1 and Isomer 2 was not determined.

Workup

  1. temperatureAfter cooling
  2. concentrationit was concentrated
  3. customto provide the product as a racemic mixture
  4. customThe individual enantiomers were separated
  5. washunder SFC conditions (Chiralcel OJ-H 5×25 cm, column temperature 20° C., isocratic elution with mobile phase 35% acetonitrile+0.1 TFA in CO2, 280 mL/min, 250 nM)
  6. customon chiral HPLC, 7.26 min
  7. customon chiral HPLC, 9.88 min

Sources & evidence

ORD record
ord-09cea3e316ce454abe8c06036ae65746
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

Loading…