Water → HCID 178462325, compound

HRID 467449Notes

Reaction equation

HRID 467449 reaction equation
[CH3:1][C@@H:2]([O:17][C@H:18]1[O:23][CH2:22][CH2:21][N:20]([CH2:24][C:25]2[NH:30][C:28](=[O:29])[N:27]([P:31]([OH:34])([OH:33])=[O:32])[N:26]=2)[C@H:19]1[C:35]1[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=1)[C:3]1[CH:4]=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.O>CO>[CH3:1][C@@H:2]([O:17][C@H:18]1[O:23][CH2:22][CH2:21][N:20]([CH2:24][C:25]2[N:30]=[C:28]([OH:29])[N:27]([P:31]([OH:33])([OH:34])=[O:32])[N:26]=2)[C@H:19]1[C:35]1[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=1)[C:3]1[CH:8]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:6]=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:4]=1

Participants

4

Reactant 2

HCID 962WaterHCID 135564864Fosaprepitant dimeglumine

Product 1

HCID 178462325HCID 178462325, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

6.0 gm of fosaprepitant dimeglumine salt, prepared as in Part B, 120 ml of water and 120 ml of methanol were charged in a clean and dry round bottom flask followed by cooling to about 0° C. The pH of the reaction mixture was adjusted to about 1 by the addition of 1N hydrochloric acid solution at about 0° C.-5° C. The resultant reaction mixture was stirred for about 5 minutes. The separated solid was filtered and the solid was washed with copious amount of water to neutral pH. Finally, the solid was washed with 12 ml of methanol followed by drying the solid obtained at about 35° C.-40° C. under vacuum to afford 2.9 gm of fosaprepitant, neutral form, having the XRPD pattern, which is substantially in accordance with FIG. 3; and a DSC thermogram, which is substantially in accordance with FIG. 4.

Workup

  1. additionwere charged in a clean and
  2. customdry round bottom flask
  3. additionThe pH of the reaction mixture was adjusted to about 1 by the addition of 1N hydrochloric acid solution at about 0° C.-5° C
  4. customThe resultant reaction mixture
  5. filtrationThe separated solid was filtered
  6. washthe solid was washed with copious amount of water to neutral pH
  7. washFinally, the solid was washed with 12 ml of methanol
  8. customby drying the solid
  9. customobtained at about 35° C.-40° C. under vacuum

Sources & evidence

ORD record
ord-0a9531920d984f7293fe34ff7e5f07f5
Source dataset
uspto-grants-2014_01
Patent number
US08623844B2

Reaction notes

Loading…