Ammonia → HCID 131734443, compound

HRID 588758Notes

Reaction equation

HRID 588758 reaction equation
[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[C:9]([O:15][CH2:16][O:17][P@@:18]([CH2:27][O:28][CH:29]([CH3:41])[CH2:30][N:31]1[CH:39]=[N:38][C:37]2[C:32]1=[N:33][CH:34]=[N:35][C:36]=2[NH2:40])([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:19])(=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11].N.[OH2:43]>>[C:1]([OH:8])(=[O:7])[C@@H:2]([C@H:3]([C:4]([OH:6])=[O:5])[OH:14])[OH:43].[C:9]([O:15][CH2:16][O:17][P@@:18]([CH2:27][O:28][C@H:29]([CH3:41])[CH2:30][N:31]1[CH:39]=[N:38][C:37]2[C:32]1=[N:33][CH:34]=[N:35][C:36]=2[NH2:40])([O:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:19])(=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 444972Fumaric AcidHCID 90118427HCID 90118427, compound

Product 1

HCID 131734443HCID 131734443, compound

Procedure

In a round bottom flask, fumaric acid salt of ((R)-((1-(6-amino-9H-purin-9-yl)propan-2-yloxy)methyl)(phenoxy)phosphoryloxy)methyl pivalate (50 g), water (500 ml) and liquid ammonia (50 ml) at 23-25° C. The reaction mass was stirred for 30 minutes and extracted with dichloromethane (500 ml). The organic layer was collected and distilled under vacuum. To the residue, 135 ml water and 27 ml acetonitrile was added. The contents were stirred at 23-25° C. for 15 minutes. L-tartaric acid (4.25 g) was added and stirred at 55-60° C. The material was filtered, washed with acetonitrile and dried at 40-45° C. to obtain ((R)—(((R)-1-(6-amino-9H-purin-9-yl)propan-2-yloxy)methyl)(phenoxy)phosphoryloxy)methyl pivalate L-tartarate. (Yield—10 g, 80% diastereomeric purity). The solid was purified with water and acetonitrile to obtain ((R)—(((R)-1-(6-amino-9H-purin-9-yl)propan-2-yloxy)methyl)(phenoxy)phosphoryloxy)methyl pivalate L-tartarate (Yield—7 g, 95% diastereomeric purity).

Workup

  1. customat 23-25° C
  2. extractionextracted with dichloromethane (500 ml)
  3. customThe organic layer was collected
  4. distillationdistilled under vacuum
  5. additionTo the residue, 135 ml water and 27 ml acetonitrile was added
  6. stirringThe contents were stirred at 23-25° C. for 15 minutes
  7. additionL-tartaric acid (4.25 g) was added
  8. stirringstirred at 55-60° C
  9. filtrationThe material was filtered
  10. washwashed with acetonitrile
  11. customdried at 40-45° C.

Sources & evidence

ORD record
ord-eb70232f5ddc42e4a6c33a5efe9b93e4
Source dataset
uspto-grants-2016_01
Patent number
US09227990B2

Reaction notes

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