Ammonia → HCID 15069964, compound

HRID 1078256Notes

Reaction equation

HRID 1078256 reaction equation
O1CCN([CH2:7][C:8]2[NH:22][C:21]3[C:23]4[C:9]=2[CH2:10][C@@H:11]2[C@@H:16]([C:17]=4[CH:18]=[CH:19][CH:20]=3)[CH2:15][C@H:14]([NH2:24])[CH2:13][N:12]2[CH2:25][CH2:26][CH3:27])CC1.Cl[O:29][C:30](C)(C)C.N.Cl.O1CCC[CH2:37]1>C(N(CC)CC)C>[CH2:25]([N:12]1[C@H:11]2[C@@H:16]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:23]=3[C:9]([CH2:10]2)=[C:8]([CH:7]=[CH2:37])[NH:22]4)[CH2:15][C@H:14]([NH:24][CH:30]=[O:29])[CH2:13]1)[CH2:26][CH3:27]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 521297Tert-Butyl hypochloriteHCID 15069961HCID 15069961, compound

Product 1

HCID 15069964HCID 15069964, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
-40 °C

Procedure

1.1 g of 2-morpholinomethyl-6-n-propyl-8alpha-ergolinylamine (3 mmol) is formylated as described in example 4, then dissolved in 50 ml of tetrahydrofuran and 1 ml of triethylamine, cooled to -40° C. and mixed with a solution of 0.5 ml of tert-butyl hypochlorite in 10 ml of tetrahydrofuran. After 30 minutes stirring, the batch is poured on ice, made alkaline with ammonia and extracted with dichloromethane. The organic phases are dried and concentrated by evaporation. The residue is dissolved in 40 ml of tetrahydrofuran and added to a Wittig reagent, which was prepared from 6 g of methyl triphenylphosphonium bromide and 2 g of potassium tert-butylate in 70 ml of tetrahydrofuran by stirring 15 minutes at -78° C. It is allowed to react for 1 hour at -78° C., then heated slowly to -40° C. and stirred for 2 hours at -40° C. Then it is mixed with hydrochloric acid solution, extracted with ethyl acetate and the organic phases dried and concentrated by evaporation. The residue is chromatographed on silica gel with dichloromethane/methanol and crystallized, yield 35%.

Workup

  1. additionthe batch is poured on ice
  2. extractionextracted with dichloromethane
  3. customThe organic phases are dried
  4. concentrationconcentrated by evaporation
  5. dissolutionThe residue is dissolved in 40 ml of tetrahydrofuran
  6. additionadded to a Wittig reagent, which
  7. customwas prepared from 6 g of methyl triphenylphosphonium bromide and 2 g of potassium tert-butylate in 70 ml of tetrahydrofuran
  8. stirringby stirring 15 minutes at -78° C
  9. customto react for 1 hour at -78° C.
  10. stirringstirred for 2 hours at -40° C
  11. extractionextracted with ethyl acetate
  12. customthe organic phases dried
  13. concentrationconcentrated by evaporation
  14. customThe residue is chromatographed on silica gel with dichloromethane/methanol
  15. customcrystallized

Sources & evidence

ORD record
ord-86e8441d6c604c6899fad9e4a4968a8c
Source dataset
uspto-grants-1996_08
Patent number
US05547958

Reaction notes

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