(+)(2aR,4S)-l-benzoyl-6-iodo-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole → (2aR,4S)-1-benzoyl-6-(2-oxazolyl)-4-(di-n-propylamino)-1,2,2a,3,4, 5-hexahydrobenz[cd]indole

HRID 55339Notes

Reaction equation

HRID 55339 reaction equation
C([Sn](CCCC)(CCCC)[C:6]1[O:7][CH:8]=[CH:9][N:10]=1)CCC.[C:19]([N:27]1[C:35]2[CH:34]=[CH:33][C:32](I)=[C:31]3[CH2:37][C@@H:38]([N:40]([CH2:44][CH2:45][CH3:46])[CH2:41][CH2:42][CH3:43])[CH2:39][C@H:29]([C:30]=23)[CH2:28]1)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1(C)C=CC=CC=1>[C:19]([N:27]1[C:35]2[CH:34]=[CH:33][C:32]([C:6]3[O:7][CH:8]=[CH:9][N:10]=3)=[C:31]3[CH2:37][C@@H:38]([N:40]([CH2:44][CH2:45][CH3:46])[CH2:41][CH2:42][CH3:43])[CH2:39][C@H:29]([C:30]=23)[CH2:28]1)(=[O:26])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 9805495(+)(2aR,4S)-l-benzoyl-6-iodo-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indoleHCID 154861832-(Tri-n-butylstannyl)oxazole

Product 1

HCID 15777987(2aR,4S)-1-benzoyl-6-(2-oxazolyl)-4-(di-n-propylamino)-1,2,2a,3,4, 5-hexahydrobenz[cd]indoleYield 67.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 5.0 g (13.8 mmol) of the crude 2-tributylstannyloxazole prepared above and 6.8 g (13.9 mmol) of (+)(2aR,4S)-1-benzoyl-6-iodo-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole in 100 ml of toluene was treated with 0.7 g (0.6 mmol) of tetrakis-(triphenylphosphine)palladium then refluxed under nitrogen for 20 hours. After cooling the reaction mixture was washed with a saturated brine solution and then dried over Na2SO4. Concentration in vacuo provided a viscous oil which was chromatographed over a silica gel column using a solvent gradient progressing from toluene to 1:1 toluene/EtOAc. The product from the column was dissolved in 1M HCl. This solution was then washed with ether, made alkaline with 5M NaOH, and extracted with CH2Cl2. Concentration of the extract in vacuo gave about 4 g of a brown oil. When this oil was dissolved in pentane a small amount of a red/brown resin separated leaving a clear, yellow solution. The resin was separated and the pentane was evaporated to provide a residue. This residue was crystallized by dissolving it in a small amount of CH2Cl2 and slowly adding isoctane. The crystalline (-)(2aR,4S)-1-benzoyl-6-(2-oxazolyl)-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole, obtained in four crops, weighed 2.63 g. m.p. 103°-104° C.

Workup

  1. temperaturethen refluxed under nitrogen for 20 hours
  2. temperatureAfter cooling the reaction mixture
  3. washwas washed with a saturated brine solution
  4. dry with materialdried over Na2SO4
  5. concentrationConcentration in vacuo
  6. customprovided a viscous oil which
  7. customwas chromatographed over a silica gel column
  8. dissolutionThe product from the column was dissolved in 1M HCl
  9. washThis solution was then washed with ether
  10. extractionextracted with CH2Cl2
  11. extractionConcentration of the extract in vacuo

Sources & evidence

ORD record
ord-a02e6ef9fced4472b51a9345c1956851
Source dataset
uspto-grants-1997_04
Patent number
US05624944

Reaction notes

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