Potassium Carbonate → 2-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-1,2,3-triazolo(4,5-d)pyrimidin-3-yl)tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl)oxy)ethanol

HRID 1045074Notes

Reaction equation

HRID 1045074 reaction equation
[CH2:1]1[C@@H:3]([NH3+:4])[C@H:2]1[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]([F:12])[CH:6]=1.C1C=CC(C(O)C([O-])=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:31]1[C:32]2[N:43]=[N:42][N:41]([C@H:44]3[C@@H:48]4[O:49][C:50]([CH3:53])([CH3:52])[O:51][C@@H:47]4[C@@H:46]([O:54][CH2:55][CH2:56][OH:57])[CH2:45]3)[C:33]=2[N:34]=[C:35]([S:37][CH2:38][CH2:39][CH3:40])[N:36]=1>O>[F:12][C:7]1[CH:6]=[C:5]([C@@H:2]2[CH2:1][C@H:3]2[NH:4][C:31]2[C:32]3[N:43]=[N:42][N:41]([C@H:44]4[C@@H:48]5[O:49][C:50]([CH3:52])([CH3:53])[O:51][C@@H:47]5[C@@H:46]([O:54][CH2:55][CH2:56][OH:57])[CH2:45]4)[C:33]=3[N:34]=[C:35]([S:37][CH2:38][CH2:39][CH3:40])[N:36]=2)[CH:10]=[CH:9][C:8]=1[F:11]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 210357742-[[(3aR,4S,6R,6aS)-6-[7-Chloro-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanolHCID 66808833trans-(1r,2s)-2-(3,4-Difluorophenyl)cyclopropanaminium (2r)-2-hydroxy-2-phenylethanoate

Product 1

HCID 672892902-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-1,2,3-triazolo(4,5-d)pyrimidin-3-yl)tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl)oxy)ethanol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

trans-(1R,2S)-2-(3,4-Difluorophenyl)cyclopropanaminium (2R)-2-hydroxy-2-phenylethanoate (258 kg) and potassium carbonate (280 kg) were dissolved in water (1024 kg) and charged to the solution of 2-({(3aR,4S,6R,6aS)-6-[7-chloro-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}oxy)ethanol solution from example 5 above with a rate that kept the temperature of the reaction ≦30° C. After full conversion was reached (≧99.9%) the water layer was separated off. The organic layer was washed with a mixture of acetic acid (96 kg) and sodium chloride (96 kg) in water (768 kg) and then washed again with a mixture of acetic acid (32 kg) and sodium chloride (22 kg) in water (952 kg). A third wash of the organic layer was done with sodium chloride (96 kg) in water (864 kg), whereafter the organic layer was used in the next step.

Workup

  1. customthe temperature of the reaction ≦30° C
  2. customwas separated off
  3. washThe organic layer was washed with a mixture of acetic acid (96 kg) and sodium chloride (96 kg) in water (768 kg)
  4. washwashed again with a mixture of acetic acid (32 kg) and sodium chloride (22 kg) in water (952 kg)
  5. washA third wash of the organic layer

Sources & evidence

ORD record
ord-40bddbef90354835b0dedf9377105dda
Source dataset
uspto-grants-2013_10
Patent number
US08563755B2

Reaction notes

Loading…