1-Butanol → HCID 178476584, compound

HRID 64392Notes

Reaction equation

HRID 64392 reaction equation
[C:1]([O:4][C@H:5]1[CH2:29][CH2:28][C@@:27]2([CH3:30])[C:7]3([O:32][C@H:8]3[CH2:9][C@@H:10]3[C@@H:26]2[CH2:25][CH2:24][C@@:23]2([CH3:31])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C@H:15]([CH3:22])[CH2:16][CH2:17][CH2:18][CH:19]([CH3:21])[CH3:20])[CH2:6]1)(=[O:3])[CH3:2].[NH2:33][CH2:34][CH2:35][C:36]1[N:40]=[CH:39][NH:38][CH:37]=1.C(O)CCC>COC(C)(C)C>[C:1]([O:4][C@H:5]1[CH2:29][CH2:28][C@@:27]2([CH3:30])[C@@:7]([OH:32])([C@H:8]([NH:33][CH2:34][CH2:35][C:36]3[N:40]=[CH:39][NH:38][CH:37]=3)[CH2:9][C@@H:10]3[C@@H:26]2[CH2:25][CH2:24][C@@:23]2([CH3:31])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C@H:15]([CH3:22])[CH2:16][CH2:17][CH2:18][CH:19]([CH3:20])[CH3:21])[CH2:6]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 2631-ButanolHCID 1317372185,6alpha-Epoxicholestan-3beta-yl acetateHCID 178419017HCID 178419017, compound

Product 1

HCID 178476584HCID 178476584, compoundYield 61.1%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

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.

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-1a8fdad506fe4c41b878ec1989b2a756
Source dataset
uspto-grants-2016_09
Patent number
US09447141B2

Reaction notes

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