Reaction #92670

ord-1a8fdad506fe4c41b878ec1989b2a756

Reaction equation

CC(=O)O[C@H]1CC[C@]2(C)[C@H]3CC[C@]4(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]4[C@@H]3C[C@@H]3OC32C1
5,6α-epoxicholestan-3β-yl acetate
NCCc1c[nH]cn1
histamine
CCCCO
1-Butanol
→
CC(=O)O[C@H]1CC[C@]2(C)[C@H]3CC[C@]4(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]4[C@@H]3C[C@@H](NCCc3c[nH]cn3)[C@@]2(O)C1
5α-Hydroxy-6β-[2-(1H-imidazol-4-yl)-ethylamino]-cholestan-3β-yl acetate
Yield 61.1%

Reactants

CC(=O)O[C@H]1CC[C@]2(C)[C@H]3CC[C@]4(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]4[C@@H]3C[C@@H]3OC32C1
5,6α-epoxicholestan-3β-yl acetate
NCCc1c[nH]cn1
histamine
CCCCO
1-Butanol

Reagents

None

Solvents

COC(C)(C)C
methyl-tertbutyl-ether

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Otherequipped with a magnetic stirrer bar
  2. 2
    Temperaturethe mixture heated
  3. 3
    Temperatureto reflux for 40 h
  4. 4
    Washwashed with water (5 vol) and with brine (5 vol)
  5. 5
    Washeluted with methyl-tertbutyl-ether (3 vol)
  6. 6
    Otherthe solvent was removed under reduced pressure

Procedure

5,6α-epoxicholestan-3β-yl acetate (9.8 g, 22.1 mmol, 1 eq) and histamine (4.9 g, 44.1 mmol, 2 eq) were charged in a round-bottomed flask equipped with a magnetic stirrer bar. 1-Butanol (70 ml, 5 vol) was added and the mixture heated to reflux for 40 h. The reaction mixture was cooled at r.t., diluted with methyl-tertbutyl-ether (5 vol) and washed with water (5 vol) and with brine (5 vol). The organic layer was passed through a silica pad (40 g) eluted with methyl-tertbutyl-ether (3 vol) then 10% Methanol/ethyl acetate (60 vol). Fractions of interest were pooled and the solvent was removed under reduced pressure to give 5α-Hydroxy-6β-[2-(1H-imidazol-4-yl)-ethylamino]-cholestan-3β-yl acetate as a white solid (7.5 g, 58%). In same conditions, use of ethanol as solvent (40 vol) and Ca(OTf)2 as catalyst gave a 14% yield.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US09447141B2uspto-grants-2016_09