Acetic Acid → 2-(((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)ethanol

HRID 589820Notes

Reaction equation

HRID 589820 reaction equation
[NH2:1][C:2]1[C:3]([NH:13][C@H:14]2[C@@H:18]3[O:19][C:20]([CH3:23])([CH3:22])[O:21][C@@H:17]3[C@@H:16]([O:24][CH2:25][CH2:26][OH:27])[CH2:15]2)=[N:4][C:5]([S:9][CH2:10][CH2:11][CH3:12])=[N:6][C:7]=1[Cl:8].C(O)(=O)C.[N:32]([O-])=O.[Na+]>O.C(OCC)(=O)C>[Cl:8][C:7]1[C:2]2[N:1]=[N:32][N:13]([C@H:14]3[C@@H:18]4[O:19][C:20]([CH3:22])([CH3:23])[O:21][C@@H:17]4[C@@H:16]([O:24][CH2:25][CH2:26][OH:27])[CH2:15]3)[C:3]=2[N:4]=[C:5]([S:9][CH2:10][CH2:11][CH3:12])[N:6]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 102021862-(((3aR,4S,6R,6aS)-6-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanolHCID 23668193Sodium Nitrite

Product 1

HCID 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)ethanol

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

A flask was charged with 2-(((3aR,4S,6R,6aS)-6-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-4H-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethan-1-ol (50 g), acetic acid (265 mL) and water (50 mL). The mixture was stirred and cooled to 0-5° C. followed by addition of aqueous sodium nitrite solution (8.65 g in 50 mL) over a period of about 1 hour. The mixture was stirred at the same temperature for about 2 hours followed by addition of ethyl acetate (250 mL) and water (250 mL). The mixture was further stirred at room temperature for about 45 minutes at which point water (250 mL) was added. The mixture was stirred and layers were separated, aqueous layer was extracted with ethyl acetate (250 mL). Total organic layer was separated and washed with aqueous potassium carbonate solution (20%, 2×250 mL). The organic layer (˜500 mL) was used for subsequent step.

Workup

  1. stirringThe mixture was stirred at the same temperature for about 2 hours
  2. additionwas added
  3. stirringThe mixture was stirred
  4. customlayers were separated
  5. extractionaqueous layer was extracted with ethyl acetate (250 mL)
  6. customTotal organic layer was separated
  7. washwashed with aqueous potassium carbonate solution (20%, 2×250 mL)

Sources & evidence

ORD record
ord-a79f0f464fbe425687511d59b5dd4f09
Source dataset
uspto-grants-2016_01
Patent number
US09233966B2

Reaction notes

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