1-Butanol → HCID 178454723, compound

HRID 64393Notes

Reaction equation

HRID 64393 reaction equation
[C:1]([O:6][C@H:7]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C:9]3([O:34][C@H:10]3[CH2:11][C@@H:12]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:33])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:24])[CH2:18][CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])[CH2:8]1)(=[O:5])[CH2:2][CH2:3][CH3:4].[NH2:35][CH2:36][CH2:37][C:38]1[N:42]=[CH:41][NH:40][CH:39]=1.C(O)CCC>COC(C)(C)C>[C:1]([O:6][C@H:7]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C@@:9]([OH:34])([C@H:10]([NH:35][CH2:36][CH2:37][C:38]3[N:42]=[CH:41][NH:40][CH:39]=3)[CH2:11][C@@H:12]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:33])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:24])[CH2:18][CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])[CH2:8]1)(=[O:5])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 2631-ButanolHCID 1317372195,6alpha-Epoxicholestan-3beta-yl butyrateHCID 178419017HCID 178419017, compound

Product 1

HCID 178454723HCID 178454723, compoundYield 60.4%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

5,6α-epoxicholestan-3β-yl butyrate (10.4 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 butyrate as a white solid (7.8 g, 57%). In same conditions, use of ethanol as solvent (40 vol) and Ca(OTf)2 as catalyst gave a 13% yield.

Workup

  1. customequipped with a magnetic stirrer bar
  2. temperaturethe mixture heated
  3. temperatureto reflux for 40 h
  4. washwashed with water (5 vol) and with brine (5 vol)
  5. washeluted with methyl-tertbutyl-ether (3 vol)
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-648338f8760e4c67b6dc39c120fff252
Source dataset
uspto-grants-2016_09
Patent number
US09447141B2

Reaction notes

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