L-Tartaric acid → (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate

HRID 2408288Notes

Reaction equation

HRID 2408288 reaction equation
[C:1]([OH:10])(=[O:9])[C@@H:2]([C@H:4]([C:6]([OH:8])=[O:7])[OH:5])[OH:3].C(O[C@H]([C@H](C(O)=O)OC(=O)C1C=CC=CC=1)C(O)=O)(=O)C1C=CC=CC=1.[CH2:37]([C:39]1[CH:40]=[CH:41][C:42]([CH2:45][CH2:46][O:47][C:48]2[CH:61]=[CH:60][C:51]([CH2:52][C@H:53]3[S:57][C:56](=[O:58])[NH:55][C:54]3=[O:59])=[CH:50][CH:49]=2)=[N:43][CH:44]=1)[CH3:38]>C1COCC1>[C:6]([C@@H:4]([C@H:2]([C:1]([OH:10])=[O:9])[OH:3])[OH:5])([OH:8])=[O:7].[CH2:37]([C:39]1[CH:40]=[CH:41][C:42]([CH2:45][CH2:46][O:47][C:48]2[CH:61]=[CH:60][C:51]([CH2:52][C@H:53]3[S:57][C:56](=[O:58])[NH:55][C:54]3=[O:59])=[CH:50][CH:49]=2)=[N:43][CH:44]=1)[CH3:38]

Participants

4

Reactant 2

HCID 444305L-Tartaric 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 86651733(5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of L-tartaric acid (2.52 g) in THF (12 mL) at 35° C. was added (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione(−)-O,O′-dibenzoyl-L-tartrate (2.0 g, d.e. >99%) to give a suspension which was allowed to cool to ambient temperature. After 90 min, the solid was collected by filtration, washed with 15 mL of THF at 0° C. and dried under vacuum to give (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate which contained 0.5 eq THF by NMR analysis (2.06 g). This product (1.0 g) was added to a solution of L-tartaric acid (1.11 g) in MeOH (10 mL) at reflux and then allowed to cool to ambient temperature with seed crystals of (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate (˜5 mg). The solid was collected by filtration, washed with 2×5 ml MeOH at 0° C. and dried under vacuum. (Method 14) 99.25%, Rt 16.22 min.; 0.75%, Rt 18.47 min.; d.e. 98.5%. (Method 2) Rt 2.87 min m/z 357 [M-C4H6O4+]. 1H NMR (400 MHz, DMSO-d6): δ 1.17 (3 H, t, J 7.4), 2.58 (2H, q, J 8.0), 3.04 (1H, dd, J 5.5, 14.2), 3.12 (2H, t, J 6.8), 3.29 (1H, dd, J 4.3, 14.2), 4.27-4.34 (4H, m), 4.86 (1H, dd, J 4.4, 9.1), 6.86 (2H, d, J 8.6), 7.13 (2H, d, J 8.6), 7.26 (1H, d, J 7.8), 7.57 (1H, dd, J 2.6, 8.3), 8.35-8.37 (1H, m).

Workup

  1. customto give a suspension which
  2. filtrationthe solid was collected by filtration
  3. washwashed with 15 mL of THF at 0° C.
  4. customdried under vacuum

Sources & evidence

ORD record
ord-b814746caa95484ea6fefa1f6f87b7c7
Source dataset
uspto-grants-2014_08
Patent number
US08815837B2

Reaction notes

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