Ammonium fluoride → N-[2-(4-chlorophenyl)ethyl]-3-{2-[(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}benzamide

HRID 1866490Notes

Reaction equation

HRID 1866490 reaction equation
[Si]([O:8][C@H:9]([C:34]1[CH:39]=[CH:38][C:37]([OH:40])=[C:36]([CH2:41][OH:42])[CH:35]=1)[CH2:10][NH:11][C:12]([CH3:33])([CH3:32])[CH2:13][C:14]1[CH:15]=[C:16]([CH:29]=[CH:30][CH:31]=1)[C:17]([NH:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)=[O:18])(C(C)(C)C)(C)C.[F-].[NH4+]>CO.O>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([CH2:21][CH2:20][NH:19][C:17](=[O:18])[C:16]2[CH:29]=[CH:30][CH:31]=[C:14]([CH2:13][C:12]([NH:11][CH2:10][C@H:9]([OH:8])[C:34]3[CH:39]=[CH:38][C:37]([OH:40])=[C:36]([CH2:41][OH:42])[CH:35]=3)([CH3:33])[CH3:32])[CH:15]=2)=[CH:23][CH:24]=1

Participants

5

Reactant 2

HCID 25516Ammonium fluorideHCID 690243723-{2-[(2R)-2-(tert-butyldimethylsilanyloxy)-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}-N-[2-(4-chlorophenyl)ethyl]benzamide

Product 1

HCID 57978282N-[2-(4-chlorophenyl)ethyl]-3-{2-[(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}benzamideYield 83.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

3-{2-[(2R)-2-(tert-butydimethylsilanyloxy)-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}-N-[2-(4-chlorophenyl)ethyl]benzamide (Preparation 38) (470 mg, 0.77 mmol) and ammonium fluoride (280 mg, 7.70 mmol) in methanol (3 ml) and water (1.7 ml) were heated to 43° C. for 18 hours. The solvent was removed in vacuo and the product purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 by volume). The resulting compound was taken up in methanol and evaporated (×3) to yield a white foam (320 mg). A small sample was recrystallised (hexane:ethyl acetate) to give a white solid (mp 139-140° C.).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe product purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 by volume)
  3. customevaporated (×3)

Sources & evidence

ORD record
ord-e78f4d9509da4483a26f569da249db7c
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

Loading…