18-Crown-6 → Tert-butyl 3-((5-cyclopropyl-3-(2-phenylcyclopropyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 1748210Notes

Reaction equation

HRID 1748210 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH:12]2[CH2:13][CH:14]([OH:16])[CH2:15][CH:9]1[CH2:10][CH2:11]2)=[O:7])([CH3:4])[CH3:3].C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+].Cl[CH2:42][C:43]1[C:44]([CH:51]2[CH2:53][CH:52]2[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[N:45][O:46][C:47]=1[CH:48]1[CH2:50][CH2:49]1>C1COCC1.O>[CH:48]1([C:47]2[O:46][N:45]=[C:44]([CH:51]3[CH2:53][CH:52]3[C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:43]=2[CH2:42][O:16][CH:14]2[CH2:15][CH:9]3[N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH:12]([CH2:11][CH2:10]3)[CH2:13]2)[CH2:50][CH2:49]1

Participants

7

Reactant 4

HCID 2855718-Crown-6HCID 21187725tert-Butyl 3-hydroxy-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 23665647Potassium tert-butoxideHCID 679836154-(Chloromethyl)-5-cyclopropyl-3-(2-phenylcyclopropyl)isoxazole

Product 1

HCID 67983745Tert-butyl 3-((5-cyclopropyl-3-(2-phenylcyclopropyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of N-Boc-nortropine (80 mg, 0.35 mmol) and 18-crown-6 (125 mg, 0.5 mmol) in THF (2.5 mL) was cooled to 0° C., treated with potassium tert-butoxide (59 mg, 0.53 mmol) and stirred for 10 min. A solution of 4-(chloromethyl)-5-cyclopropyl-3-(2-phenylcyclopropyl)isoxazole (80 mg, 0.29 mmol) in THF (0.5 mL) was added and the resulting mixture stirred at rt for 2 h and then poured into water and extracted with EtOAc. The organic layer was collected, washed with brine, dried over Na2SO4, filtered, concentrated to yield tert-butyl 3-((5-cyclopropyl-3-(2-phenylcyclopropyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate. MS m/z 409.1 (M−56+1).

Workup

  1. stirringthe resulting mixture stirred at rt for 2 h
  2. extractionextracted with EtOAc
  3. customThe organic layer was collected
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1f59d8c882a5433987afae1217392221
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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