Hydrochloric Acid → 4-[4-(4,5-Dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]-1,2,3,6-tetrahydro-1-(phenylmethyl)pyridine

HRID 1528555Notes

Reaction equation

HRID 1528555 reaction equation
[C:1]1([CH:7]2[O:11][N:10]=[C:9]([C:12]3[N:13]=[C:14]([C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[S:15][CH:16]=3)[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[BH4-].[Na+].Cl>C1(C)C=CC=CC=1.O>[C:1]1([CH:7]2[O:11][N:10]=[C:9]([C:12]3[N:13]=[C:14]([C:17]4[CH2:18][CH2:19][N:20]([CH2:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:21][CH:22]=4)[S:15][CH:16]=3)[CH2:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 4311764Sodium borohydrideHCID 687460464-[4-(4,5-Dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]pyridine2×

Product 1

HCID 687439224-[4-(4,5-Dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]-1,2,3,6-tetrahydro-1-(phenylmethyl)pyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-[4-(4,5-dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]pyridine (i.e. the product of Example 13, Step A) (0.60 g, 1.95 mmol) in toluene (10 mL) was added benzyl bromide (0.670 g, 3.90 mmol), and the reaction mixture was heated to 100° C. for 12 h. Then the reaction mixture was cooled to room temperature. The solid that precipitated out was filtered and dried. The solid was dissolved in methanol (10 mL), and sodium borohydride (0.072 g, 1.95 mmol) was added in portions. The reaction mixture was stirred at room temperature for 2 h, diluted with water (50 mL), neutralized with 1.5 N aqueous hydrochloric acid solution, and extracted with ethyl acetate (50 mL). The organic layer was separated, washed with brine (25 mL), and concentrated under reduced pressure. The residue was purified by medium-pressure liquid chromatography using 3% of methanol in chloroform as eluant to give 0.4 g of the title compound as a white solid.

Workup

  1. temperatureThen the reaction mixture was cooled to room temperature
  2. customThe solid that precipitated out
  3. filtrationwas filtered
  4. customdried
  5. dissolutionThe solid was dissolved in methanol (10 mL)
  6. extractionextracted with ethyl acetate (50 mL)
  7. customThe organic layer was separated
  8. washwashed with brine (25 mL)
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by medium-pressure liquid chromatography

Sources & evidence

ORD record
ord-8ea16faf1c37487380246de7ab5cd9b9
Source dataset
uspto-grants-2015_07
Patent number
US09090604B2

Reaction notes

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