Hydrochloric Acid → HCID 57898982, compound

HRID 911047Notes

Reaction equation

HRID 911047 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1.Cl.[CH3:13][C:14]1[N:15]=[C:16]([NH:19][C:20]2[CH:25]=[C:24]([O:26][C:27]3[CH:28]=[C:29]([CH:35]=[CH:36][CH:37]=3)[O:30][CH2:31][C:32](O)=[O:33])[CH:23]=[CH:22][N:21]=2)[S:17][CH:18]=1.Cl>CCOCC>[CH3:13][C:14]1[N:15]=[C:16]([NH:19][C:20]2[CH:25]=[C:24]([O:26][C:27]3[CH:28]=[C:29]([CH:35]=[CH:36][CH:37]=3)[O:30][CH2:31][CH2:32][OH:33])[CH:23]=[CH:22][N:21]=2)[S:17][CH:18]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 24826503HCID 24826503, compound

Product 1

HCID 57898982HCID 57898982, compoundYield 19.6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

Lithium aluminum hydride in ether (1.0 M, 3.86 ml, 3.86 mmol) was added to a solution of THF (50 mL) at 0° C., 2-(3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)phenoxy)acetic acid hydrochloride (Example 66; 0.380 g, 0.965 mmol) was added portionwise. The reaction was stirred for one hour, and then quenched with an excess of solid saturated sodium sulfate decahydrate. The reaction was stirred overnight and filtered, and the solid cake was washed several times with THF. The combined filtrates were concentrated and the residue was purified by MPLC (Biotage), eluting with ethyl acetate to afford the product as the free base. The free base was dissolved in ether, and 1M HCl in ether was added. The mixture was diluted with hexanes, filtered, and washed with hexanes to afford the title compound (0.065 g, 17.7% yield) as a white powder. 1H NMR (d6-DMSO) δ 2.22 (s, 3H), 3.66 (t, 2H), 3.95 (t, 2H), 6.60-6.76 (m, 5H), 6.85 (d, 1H), 7.35 (t, 1H), 8.19 (d, 1H).

Workup

  1. customquenched with an excess of solid saturated sodium sulfate decahydrate
  2. stirringThe reaction was stirred overnight
  3. filtrationfiltered
  4. washthe solid cake was washed several times with THF
  5. concentrationThe combined filtrates were concentrated
  6. customthe residue was purified by MPLC (Biotage)
  7. washeluting with ethyl acetate
  8. customto afford the product as the free base
  9. filtrationfiltered
  10. washwashed with hexanes

Sources & evidence

ORD record
ord-374a02c14f3341d1934827aafe17d354
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

Loading…