3,5-Dimethyl-4-hydroxybenzaldehyde → 1-[(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-2-hydroxybutyl]-4-[(S)-3,5-dimethyl-4-(N-tert-butoxycarbonylpyrrolidine-2-carbonyloxy)benzyl]-1H-[1,2,4]triazol-4-ium bromide

HRID 1075426Notes

Reaction equation

HRID 1075426 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:31])([CH2:25][N:26]1[CH:30]=[N:29][CH:28]=[N:27]1)[C@H:10]([C:12]1[S:13][CH:14]=[C:15]([C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)[N:16]=1)[CH3:11].[CH3:32][C:33]1[CH:34]=[C:35]([CH:38]=[C:39]([CH3:56])[C:40]=1[O:41][C:42]([C@@H:44]1[CH2:48][CH2:47][CH2:46][N:45]1[C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[O:43])[CH2:36][Br:37].CC1C=C(C=C(C)C=1O)C=O>C(#N)C>[Br-:37].[C:21]([C:20]1[CH:19]=[CH:18][C:17]([C:15]2[N:16]=[C:12]([C@H:10]([CH3:11])[C@:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])([OH:31])[CH2:25][N:26]3[CH:30]=[N+:29]([CH2:36][C:35]4[CH:38]=[C:39]([CH3:56])[C:40]([O:41][C:42]([C@@H:44]5[CH2:48][CH2:47][CH2:46][N:45]5[C:49]([O:51][C:52]([CH3:54])([CH3:53])[CH3:55])=[O:50])=[O:43])=[C:33]([CH3:32])[CH:34]=4)[CH:28]=[N:27]3)[S:13][CH:14]=2)=[CH:24][CH:23]=1)#[N:22]

Participants

5

Reactant 3

HCID 752223,5-Dimethyl-4-hydroxybenzaldehydeHCID 467825RavuconazoleHCID 676181073,5-dimethyl-4-[(S)-N-tert-butoxycarbonylpyrrolidine-2-carbonyloxy]benzyl bromide

Product 1

HCID 110618711-[(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-2-hydroxybutyl]-4-[(S)-3,5-dimethyl-4-(N-tert-butoxycarbonylpyrrolidine-2-carbonyloxy)benzyl]-1H-[1,2,4]triazol-4-ium bromideYield 93.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1.06 g of (1R,2R)-4-[2-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl]thiazol-4-yl]benzonitrile and 1.1 g of 3,5-dimethyl-4-[(S)-N-tert-butoxycarbonylpyrrolidine-2-carbonyloxy]benzyl bromide, prepared from 3,5-dimethyl-4-hydroxybenzaldehyde in 3 steps, in 20 mL of acetonitrile was stirred for 15 h at reflux temperature and then concentrated. The residue was chromatographed on silica gel (Wakogel C-200, solvent: CH2Cl2 /MeOH=12/1) to give 1.92 g (94%y.) of 1-[(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-2-hydroxybutyl]-4-[(S)-3,5-dimethyl-4-(N-tert-butoxycarbonylpyrrolidine-2-carbonyloxy)benzyl]-1H-[1,2,4]triazol-4-ium bromide as a white solid.

Workup

  1. temperatureat reflux temperature
  2. concentrationconcentrated
  3. customThe residue was chromatographed on silica gel (Wakogel C-200, solvent: CH2Cl2 /MeOH=12/1)

Sources & evidence

ORD record
ord-944c81d361784afb9fbef2441c7ada99
Source dataset
uspto-grants-1999_05
Patent number
US05900486

Reaction notes

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