Citric Acid → Tofacitinib Citrate

HRID 1775136Notes

Reaction equation

HRID 1775136 reaction equation
[CH3:1][C@H:2]1[C@@H:7]([N:8]([C:10]2[N:18]=[CH:17][N:16]=[C:15]3[C:11]=2[CH:12]=[CH:13][NH:14]3)[CH3:9])[CH2:6][N:5]([C:19]([CH2:21][C:22]#[N:23])=[O:20])[CH2:4][CH2:3]1.Cl.[C:25]([OH:37])(=[O:36])[CH2:26][C:27]([CH2:32][C:33]([OH:35])=[O:34])([C:29]([OH:31])=[O:30])[OH:28].C(NC(C)C)(C)C>O>[CH3:1][C@H:2]1[C@@H:7]([N:8]([C:10]2[N:18]=[CH:17][N:16]=[C:15]3[C:11]=2[CH:12]=[CH:13][NH:14]3)[CH3:9])[CH2:6][N:5]([C:19]([CH2:21][C:22]#[N:23])=[O:20])[CH2:4][CH2:3]1.[CH2:32]([C:27]([OH:28])([C:29]([OH:31])=[O:30])[CH2:26][C:25]([OH:37])=[O:36])[C:33]([OH:35])=[O:34]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 7912DiisopropylamineHCID 131734729HCID 131734729, compound

Product 1

HCID 10174505Tofacitinib CitrateYield 92%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

Form APO-A tofacitinib hydrochloride (0.80 g, 2.29 mmol) was dissolved in water (0.80 mL). A solution of citric acid (0.53 g, 2.75 mmol) and N,N-diisopropylamine (0.25 g, 2.52 mmol) in water (8 mL) was charged under stirring at room temperature. Solids started to form 1-2 minutes following addition. The suspension was stirred at room temperature for 4 hours then filtered and washed with water (2×5 mL) and acetone (1×3 mL). The filtered solids were dried under vacuum (35 torr) at 40° C. for approximately 5 hours to yield tofacitinib citrate (1.06 g; 92%) as a white solid.

Workup

  1. customto form 1-2 minutes
  2. additionaddition
  3. stirringThe suspension was stirred at room temperature for 4 hours
  4. filtrationthen filtered
  5. washwashed with water (2×5 mL) and acetone (1×3 mL)
  6. customThe filtered solids were dried under vacuum (35 torr) at 40° C. for approximately 5 hours

Sources & evidence

ORD record
ord-41d156483de34672aa5103037b709002
Source dataset
uspto-grants-2016_02
Patent number
US09260438B2

Reaction notes

Loading…