Acetic Acid → HCID 22911519, compound

HRID 1378500Notes

Reaction equation

HRID 1378500 reaction equation
O1[C:6]2[CH:7]=[CH:8][C:9]([C:11]3[CH:15]=[C:14]([CH:16]4[CH2:21]CNCC4)ON=3)=[CH:10][C:5]=2OCC1.CC(C)(O[C:26]([N:28]1[CH2:33][CH2:32][CH:31]([C:34]2[CH:38]=[C:37]([C:39]3[CH:48]=[CH:47][C:42]4[O:43][CH2:44][CH2:45][O:46][C:41]=4[CH:40]=3)[O:36][N:35]=2)[CH2:30][CH2:29]1)=O)C.C1(CC=O)C2C(=CC=CC=2)C=CC=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[C:16]1([CH2:21][CH2:26][N:28]2[CH2:33][CH2:32][CH:31]([C:34]3[CH:38]=[C:37]([C:39]4[CH:48]=[CH:47][C:42]5[O:43][CH2:44][CH2:45][O:46][C:41]=5[CH:40]=4)[O:36][N:35]=3)[CH2:30][CH2:29]2)[C:10]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:11]=[CH:15][CH:14]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 12570786(Naphthalen-1-yl)acetaldehydeHCID 53964095HCID 53964095, compoundHCID 67622141HCID 67622141, compound

Product 1

HCID 22911519HCID 22911519, compound

Procedure

To 25 mL round bottomed flask with a stirring bar and an argon inlet was added 4-(3-(1,4-benzodioxan-6-yl)isoxazol-5-yl)piperdine and 1-(1,1-dimethylethoxy-carbonyl)-4-(5-(1,4-benzodioxan-6-yl)isoxazol-3-yl)piperdine (231 mg, 0.809 mmol), 1-naphthylacetaldehyde (165.3 mg, 0.971 mmol) 1,2-dichloroethane (5 mL), glacial acetic acid (55.6 ml, 0.971 mmol) and sodium triacetoxyborohydride (411.6 mg 1.942 mmol). This mixture was stirred at room temperature for 24 h then quenched with saturated aqueous sodium bicarbonate (75 ml), extracted with EtOAc (3×75 ml) washed with brine, dried (Na2SO4) and filtered. Removal of the solvent in vacuo gave a tan oil. This material was chromatographed on silica gel using 3% 2-propanol in NH3 saturated CHCl3 as eluant. The major regioisomer was obtained as an oil (upper Rf) which was crystallized from EtOAc as the hydrochloride salt, 1-(2-(1-naphthyl)ethyl)-4-(3-(1,4-benzodioxan-6-yl)isoxazol-5-yl)piperdine hydrochloride, mp 239.5°-241° C. FAB MS data are consistent with theoretical m/e=441. 1H NMR free base (CDCl3): d 1.90 (m, 2H); 2.13 (br d, J=11.5 Hz, 2H); 2.25 (br t, J=9.5 Hz, 2H); 2.78 (m, 1H), 3.16 (br d, J=11.6 Hz, 2H); 3.31 (m, 2H); 4.28 (s, 4H); 6.46 (s, 1H); 6.92 (d, J=8.2 Hz, 1H); 7.25-7.54 (m, 7H); 7.73 (d, J=8.1 Hz, 1H); 7.86 (dd, J=1.5, 8.3 Hz, 1H); 8.07 (d, J=8.4 Hz, 1H).

Workup

  1. customthen quenched with saturated aqueous sodium bicarbonate (75 ml)
  2. extractionextracted with EtOAc (3×75 ml)
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customRemoval of the solvent in vacuo
  7. customgave a tan oil
  8. customThis material was chromatographed on silica gel using 3% 2-propanol in NH3 saturated CHCl3 as eluant
  9. customThe major regioisomer was obtained as an oil (upper Rf) which
  10. customwas crystallized from EtOAc as the hydrochloride salt, 1-(2-(1-naphthyl)ethyl)-4-(3-(1,4-benzodioxan-6-yl)isoxazol-5-yl)piperdine hydrochloride, mp 239.5°-241° C

Sources & evidence

ORD record
ord-ba434c1059e743b3a9df7dc851bf745b
Source dataset
uspto-grants-1997_09
Patent number
US05668148

Reaction notes

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