1,1-Dichloroethane → HCID 67171032, compound

HRID 1506358Notes

Reaction equation

HRID 1506358 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](N1CCOCC1)=[CH:7][CH2:6][CH2:5]2.[OH:18][N:19]=[C:20](Cl)[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH3:29])=[CH:23][CH:22]=1.ClC(Cl)C.C(O)(C(F)(F)F)=O>ClCCl.C(N(CC)CC)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]1[O:18][N:19]=[C:20]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH3:29])=[CH:23][CH:22]=3)[C:7]=1[CH2:6][CH2:5]2

Participants

7

Reactant 4

HCID 63651,1-DichloroethaneHCID 6422Trifluoroacetic acidHCID 67168817HCID 67168817, compoundHCID 86669882HCID 86669882, compound

Product 1

HCID 67171032HCID 67171032, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To 4-(6-bromo-3,4-dihydronaphthalen-1-yl)morpholine (Preparation 20A, 0.36 g, 1.224 mmol) in dichloromethane (4 mL) was added N-hydroxy-4-propylbenzimidoyl chloride (Preparation 20B, 0.242 g, 1.224 mmol) dissolved in 1 mL of dichloromethane at room temperature. Next, triethylamine was added dropwise over a period of 5 min. at room temperature. The reaction mixture was stirred at room temperature for 14 h. and concentrated. The reaction mixture was partitioned between ethyl acetate (15 mL) and water (10 mL). The ethyl acetate layer was dried over sodium sulfate, filtered, and concentrated to yield an oil. To the oil was added dichloroethane (4.00 mL) followed by TFA (0.141 mL, 1.836 mmol) at room temperature. The reaction mixture was heated at 70° C. for 45 min., stirred at room temperature for 2 h, and partitioned between dichloromethane (10 mL) and sat. aq. sodium bicarbonate (10 mL). The dichloromethane layer was dried over sodium sulfate, concentrated, and purified by silica gel column chromatography employing hexane/ethyl acetate. The desired fractions were collected and concentrated to yield 7-bromo-3-(4-propylphenyl)-4,5-dihydronaphtho[2,1-d]isoxazole (0.32 g, 0.869 mmol, 71.0% yield) as a white solid. LCMS M+1=369.

Workup

  1. concentrationconcentrated
  2. customThe reaction mixture was partitioned between ethyl acetate (15 mL) and water (10 mL)
  3. dry with materialThe ethyl acetate layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield an oil
  7. temperatureThe reaction mixture was heated at 70° C. for 45 min.
  8. stirringstirred at room temperature for 2 h
  9. custompartitioned between dichloromethane (10 mL) and sat. aq. sodium bicarbonate (10 mL)
  10. dry with materialThe dichloromethane layer was dried over sodium sulfate
  11. concentrationconcentrated
  12. custompurified by silica gel column chromatography
  13. customThe desired fractions were collected
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-2aa59ba4ae0540018e2611fcd4b6b463
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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