Ammonium Chloride → Methyl 5-((3R*,4S*)-4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-3-(1-hydroxyethyl)thiophene-2-carboxylate

HRID 43947Notes

Reaction equation

HRID 43947 reaction equation
[CH3:1][Mg]Br.[CH2:4]([O:11][C:12]([NH:14][C@H:15]1[CH2:20][CH2:19][N:18]([C:21]2[S:25][C:24]([C:26]([O:28][CH3:29])=[O:27])=[C:23]([CH:30]=[O:31])[CH:22]=2)[CH2:17][C@H:16]1[O:32][CH3:33])=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[Cl-].[NH4+]>C1COCC1>[CH2:4]([O:11][C:12]([NH:14][C@H:15]1[CH2:20][CH2:19][N:18]([C:21]2[S:25][C:24]([C:26]([O:28][CH3:29])=[O:27])=[C:23]([CH:30]([OH:31])[CH3:1])[CH:22]=2)[CH2:17][C@H:16]1[O:32][CH3:33])=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 86648831Methyl cis(+/-)-5-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-3-formylthiophene-2-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 68405949Methyl 5-((3R*,4S*)-4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-3-(1-hydroxyethyl)thiophene-2-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methylmagnesium bromide (0.97 mol/L) in THF (1.59 mL, 1.54 mmol) was added to a solution of methyl cis(±)-5-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-3-formylthiophene-2-carboxylate obtained in Example (246c) (333 mg, 0.77 mmol) in THF (8 mL) at 0° C., and the mixture was stirred at room temperature for five hours. Saturated ammonium chloride solution was added to the reaction solution, and the reaction solution was extracted with ethyl acetate. The combined organic layers were washed with brine and then dried over anhydrous magnesium sulfate. Following filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=1/1) to obtain 223 mg of the title compound as a pale yellow solid (65%).

Workup

  1. extractionthe reaction solution was extracted with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-705e4759c8214193ad5d74f09f1ded9d
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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