Hydrochloric Acid → Pioglitazone hydrochloride, (R)-

HRID 2408287

Reaction equation

HRID 2408287 reaction equation
C(O[C@H]([C@H](C(O)=O)OC(=O)C1C=CC=CC=1)C(O)=O)(=O)C1C=CC=CC=1.[CH2:27]([C:29]1[CH:30]=[CH:31][C:32]([CH2:35][CH2:36][O:37][C:38]2[CH:51]=[CH:50][C:41]([CH2:42][C@H:43]3[S:47][C:46](=[O:48])[NH:45][C:44]3=[O:49])=[CH:40][CH:39]=2)=[N:33][CH:34]=1)[CH3:28].[ClH:52]>CO>[ClH:52].[CH2:27]([C:29]1[CH:30]=[CH:31][C:32]([CH2:35][CH2:36][O:37][C:38]2[CH:51]=[CH:50][C:41]([CH2:42][C@H:43]3[S:47][C:46](=[O:48])[NH:45][C:44]3=[O:49])=[CH:40][CH:39]=2)=[N:33][CH:34]=1)[CH3:28]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 53343681(5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione (-)-O,O'-dibenzoyl-L-tartrate

Product 1

HCID 53358444Pioglitazone hydrochloride, (R)-

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The product from Example 15, Step 3 was dissolved in MeOH (2.25 mL) containing 37% HCl (0.134 mL) at 35° C. The solution was filtered, EtOAc (9 mL) was poured into the stirred solution and the mixture stirred for 20 min. The white solid was collected by filtration, washed with EtOAc and dried at 30° C. under high vacuum to give the title compound (0.181 g). (Method 1) 98.3%, Rt 10.65 min.; 1.7%, Rt 14.83 min e.e. 96.6%. LCMS (Method 2): Rt 2.90 min 99.39%, m/z 357 [MH+—HCl]. LCMS (Method 3) Rt 2.91 min, m/z 357 [MH+—HCl]. 1H NMR (400 MHz, DMSO-d6): δ 12.0 (1 H, s), 8.70 (1 H, d, J 1.7 Hz), 8.36 (1 H, bd, J 8.3 Hz), 7.93 (1 H, d, J 8.2 Hz), 7.15, 6.87 (4 H, A2B2q, J 8.7 Hz), 4.86 (1 H, dd, J 4.4, 8.9 Hz), 4.38 (2 H, t, J 6.3 Hz), 3.44 (2 H, t, J 6.2 Hz), 3.29 (1 H, dd, J 4.3, 14.2 Hz), 3.06 (1 H, dd, J 9.0, 14.3 Hz), 2.78 (2 H, q, J 7.6 Hz), 1.23 (3 H, t, J 7.6 Hz).

Workup

  1. filtrationThe solution was filtered
  2. additionEtOAc (9 mL) was poured into the stirred solution
  3. filtrationThe white solid was collected by filtration
  4. washwashed with EtOAc
  5. customdried at 30° C. under high vacuum

Sources & evidence

ORD record
ord-c833079e1ef0408eba2c076a364e5330
Source dataset
uspto-grants-2014_08
Patent number
US08815837B2

Linked notes

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