Posaconazole → Dibenzyl ether

HRID 512800Notes

Reaction equation

[CH3:1][CH2:2][C@H:3]([N:7]1[N:12]=[CH:11][N:10]([C:13]2[CH:14]=[CH:15][C:16]([N:19]3[CH2:24][CH2:23][N:22]([C:25]4[CH:26]=[CH:27][C:28]([O:31][CH2:32][C@@H:33]5[CH2:37][O:36][C@:35]([C:44]6[CH:45]=[CH:46][C:47]([F:51])=[CH:48][C:49]=6[F:50])([CH2:38][N:39]6[N:43]=[CH:42][N:41]=[CH:40]6)[CH2:34]5)=[CH:29][CH:30]=4)[CH2:21][CH2:20]3)=[CH:17][CH:18]=2)[C:8]1=[O:9])[C@@H:4]([OH:6])[CH3:5].[CH2:52](O[C@H]([C@H](N1C(=O)N(C2C=CC(N3CCN(C4C=CC(O)=CC=4)CC3)=CC=2)C=N1)CC)C)[C:53]1C=CC=C[CH:54]=1>>[CH2:35]([O:36][CH2:37][C:33]1[CH:32]=[CH:54][CH:53]=[CH:52][CH:34]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.[CH3:1][CH2:2][C@H:3]([N:7]1[N:12]=[CH:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:20][CH2:21][N:22]([C:25]4[CH:26]=[CH:27][C:28]([O:31][CH2:32][C@@H:33]5[CH2:37][O:36][C@:35]([C:44]6[CH:45]=[CH:46][C:47]([F:51])=[CH:48][C:49]=6[F:50])([CH2:38][N:39]6[N:43]=[CH:42][N:41]=[CH:40]6)[CH2:34]5)=[CH:29][CH:30]=4)[CH2:23][CH2:24]3)=[CH:15][CH:14]=2)[C:8]1=[O:9])[C@@H:4]([OH:6])[CH3:5]

Participants

Reactant 2

HCID 468595Posaconazole

HCID 78577436Posaconazole Impurity 3

Product 2

HCID 7657Dibenzyl ether

HCID 468595Posaconazole

Procedure

U.S. Pat. No. 5,625,064 discloses a process for the preparation of posaconazole which involves the condensation of 1-((2S,3R)-2-(benzyloxy)pentan-3-yl)-4-(4-(4-(4-hydroxyphenyl)piperazin-1-yl)phenyl)-1H-1,2,4-triazol-5(4H)-one with (−)-(5R-cis)-5-(2,4-difluorophenyl)-5-[1,2,4]triazol-1-ylmethyl-tetrahydro-3-furanmethylester derivative in the presence of a base to give benzyl ether of posaconazole which is then deprotected either with palladium on carbon in the presence of formic acid or aqueous hydrobromic acid to form posaconazole.

Sources & evidence

ORD record: ord-f3f265dc173646b0a109c8dbeffb9640
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102664B2

Reaction notes

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