Methanol → Voriconazole (1R)-(-)-10-camphorsulfonate

HRID 1099517Notes

Reaction equation

HRID 1099517 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([O-])(=O)C.[Na+].[C@@:31]12([CH2:41][S:42]([OH:45])(=[O:44])=[O:43])[C:38]([CH3:40])([CH3:39])[CH:35]([CH2:36][CH2:37]1)[CH2:34][C:32]2=[O:33].CO>C(O)C.[Pd]>[C@@:31]12([CH2:41][S:42]([O:25][C@@:10]([C:17]3[CH:18]=[CH:19][C:20]([F:24])=[CH:21][C:22]=3[F:23])([C@H:2]([C:3]3[C:4]([F:9])=[CH:5][N:6]=[CH:7][N:8]=3)[CH3:1])[CH2:11][N:12]3[CH:13]=[N:14][CH:15]=[N:16]3)(=[O:44])=[O:43])[C:38]([CH3:40])([CH3:39])[CH:35]([CH2:36][CH2:37]1)[CH2:34][C:32]2=[O:33].[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@@:31]12([CH2:41][S:42]([O-:45])(=[O:43])=[O:44])[C:38]([CH3:40])([CH3:39])[CH:35]([CH2:36][CH2:37]1)[CH2:34][C:32]2=[O:33]

Participants

8

Reactant 4

HCID 887MethanolHCID 71616Voriconazole4×HCID 131278(R)-camphorsulfonic acidHCID 517045Sodium Acetate

Product 2

HCID 86626425Voriconazole (1R)-(-)-10-camphorsulfonateHCID 131729536HCID 131729536, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Preparation of Racemic Voriconazole (Compound V) from Enantiomeric Pair B of chloroderivative of formula (IV) by classical hydrogenation conditions using Pd/C and sodium acetate in ethanol is shown in scheme 2. Resolution of the obtained racemic Voriconazole (compound V) is performed with (1R)-(−)-10-camphorsulfonic acid (CSA) in 38 volumes of methanol to give (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol (1R)-(−)-10-camphorsulfonate (compound VI), that is, Voriconazole (1R)-(−)-10-camphorsulfonate, as hemimethanolate having a melting point of 176° C. Voriconazole (compound I) is isolated from Voriconazole (1R)-(−)-10-camphorsulfonate (compound VI) using dichloromethane and saturated aqueous sodium bicarbonate and final evaporation of the organic extract. The obtained Voriconazole shows a melting point of 127° C.

Sources & evidence

ORD record
ord-5c9688cdd85444dfbfad21278fa3b56a
Source dataset
uspto-grants-2012_03
Patent number
US08143397B2

Reaction notes

Loading…