Acetic Acid → tert-butyl 2-[(hydroxyamino)carbonyl]-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate

HRID 468679Notes

Reaction equation

HRID 468679 reaction equation
[S:1]1[C:9]2[CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5][C:4]=2[CH:3]=[C:2]1[C:17]([O:19]CC)=O.Cl.[NH2:23][OH:24].[OH-].[K+].C(O)(=O)C>CO>[OH:24][NH:23][C:17]([C:2]1[S:1][C:9]2[CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5][C:4]=2[CH:3]=1)=[O:19]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 118454155-tert-Butyl 2-ethyl 6,7-dihydrothieno[3,2-c]pyridine-2,5(4H)-dicarboxylate

Product 1

HCID 58157578tert-butyl 2-[(hydroxyamino)carbonyl]-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylateYield 50.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 5-tert-butyl 2-ethyl 6,7-dihydrothieno[3,2-c]pyridine-2,5(4H)-dicarboxylate (0.056 g, 0.18 mmol; prepared as described in J. Med. Chem. 2006, 49(15): 4623), hydroxylamine hydrochloride (0.037 mg, 0.54 mmol) and potassium hydroxide (0.1 mg, 1.8 mmol) in methanol (2 mL) was heated at 75° C. for 1 hour. Upon cooling to room temperature the reaction was quenched by the addition of acetic acid (100 μL, 1.8 mmol) and the solvent was evaporated to dryness. The residue was dissolved in DMSO (1 mL) and purified using a Gilson prep to afford a white solid (26.9 mg, 50%). LCMS (FA) ES+ 299; 1H NMR (400 MHz, MeOD) δ 7.27 (s, 1H), 4.46 (s, 2H), 3.71 (t, J=5.4 Hz, 2H), 2.84 (t, J=5.7 Hz, 2H), 1.48 (s, 9H).

Workup

  1. temperatureUpon cooling to room temperature the reaction
  2. customthe solvent was evaporated to dryness
  3. dissolutionThe residue was dissolved in DMSO (1 mL)
  4. custompurified

Sources & evidence

ORD record
ord-436c8212ccec4852b8b5dcdf3fc92dde
Source dataset
uspto-grants-2014_01
Patent number
US08624040B2

Reaction notes

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