Hydrochloric Acid → HCID 56832761, compound

HRID 2402125Notes

Reaction equation

HRID 2402125 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:17]3[CH2:18][CH2:19][O:20][CH2:21][CH:22]=3)[S:10][C:11]=2[C:12]([O:14]CC)=[O:13])=[CH:4][CH:3]=1.O1CCCC1.CO.[OH-].[Li+].Cl>CCOC(C)=O>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:17]3[CH2:18][CH2:19][O:20][CH2:21][CH:22]=3)[S:10][C:11]=2[C:12]([OH:14])=[O:13])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 66749676HCID 66749676, compound

Product 1

HCID 56832761HCID 56832761, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

In a round bottom flask equipped with a stir bar, a solution of ethyl 4-(4-chlorobenzyl)-2-(3,6-dihydro-2H-pyran-4-yl)-1,3-thiazole-5-carboxylate (109 mg, 0.300 mmol) in tetrahydrofuran (3.33 mL, 41.1 mmol) and methanol (1.67 mL, 41.1 mmol) was treated with lithium hydroxide (1.0M in water, 2.40 mL, 2.40 mmol). The mixture was stirred at room temperature overnight. pH was adjusted to −3 via addition of 1N aqueous HCl solution, and the reaction was then diluted with EtOAc and transferred to separatory funnel. The layers were separated, and the aqueous layer was extracted 2× with EtOAc. Combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Column chromatography (gradient elution, 0 to 10% MeOH in DCM) afforded 4-(4-chlorobenzyl)-2-(3,6-dihydro-2H-pyran-4-yl)-1,3-thiazole-5-carboxylic acid (100) (53 mg, yield 53% as a white powder. LCMS: (FA) ES+ 336; 1H NMR (400 MHz, DMSO) δ 13.52 (bs, 1H), 7.35-7.31 (m, 2H), 7.27-7.23 (m, 2H), 6.82-6.79 (m, 1H), 4.40 (s, 2H), 4.24-4.22 (m, 2H), 3.77 (t, J=5.4, 2H), 2.50-2.45 (m, 2H).

Workup

  1. customIn a round bottom flask equipped with a stir bar
  2. customtransferred to separatory funnel
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted 2× with EtOAc
  5. washCombined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. washColumn chromatography (gradient elution, 0 to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-5fc09b70b3b9441f88205fb6dc486b60
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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