Voriconazole → Voriconazole

HRID 1099518Notes

Reaction equation

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

Participants

Reactant 2

HCID 71616Voriconazole2×

HCID 131278(R)-camphorsulfonic acid

Product 2

HCID 71616Voriconazole

HCID 86626425Voriconazole (1R)-(-)-10-camphorsulfonate

Procedure

More specifically, the invention relates to a process which comprises the dehalogenation of a haloderivative of Voriconazole via catalytic transfer hydrogenation of i.e (2R,3S/2S,3R)-3-(4-halo-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol to obtain racemic Voriconazole (i.e (2R,3S/2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol). Thereafter, racemic Voriconazole (compound V) is resolved using (1R)-(−)-10-camphorsulfonic acid ((−)-CSA) and isolating Voriconazole (compound I) from the diastereomeric salt Voriconazole (1R)-(−)-10-camphorsulfonate (compound VI).

Sources & evidence

ORD record: ord-008b36442fda4e2795a1af760c4863ff
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143397B2

Reaction notes

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