Hydrochloric Acid → HCID 86657800, compound

HRID 401950Notes

Reaction equation

HRID 401950 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14]COC)[C@H:10]([CH2:18][O:19][C:20]2[N:21]=[N:22][C:23]([CH2:39][CH2:40][CH2:41][CH3:42])=[C:24]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH:33]4[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]4)=[CH:28][CH:27]=3)[CH:25]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl>CO.C(Cl)Cl.O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([OH:14])[C@H:10]([CH2:18][O:19][C:20]2[N:21]=[N:22][C:23]([CH2:39][CH2:40][CH2:41][CH3:42])=[C:24]([C:26]3[CH:27]=[CH:28][C:29]([O:32][CH:33]4[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]4)=[CH:30][CH:31]=3)[CH:25]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 86657799HCID 86657799, compound

Product 1

HCID 86657800HCID 86657800, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of (±)-cis-3-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-4-methoxymethoxy-piperidine-1-carboxylic acid tert-butyl ester (1.59 mmol, 0.93 g) in a mixture of methanol (2 mL) and DCM (0.5 mL) was added 4 N HCl in dioxane (5 mL) at room temperature and continued stirring for 1 h. The progress of the reaction was monitored by LCMS analysis of an aliquot of the reaction mixture. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in DCM (5 mL) and added 2 N sodium hydroxide solution (2 mL) followed by di-t-butyl dicarbonate (1 g) and the resultant reaction mixture was stirred at room temperature for 2 h. The organic layer was separated and the aqueous layer was extracted with DCM (5 mL). The combined organic layer was concentrated under reduced pressure and the residue was purified by silica gel flash column chromatography by eluting with 50% ethyl acetate in hexanes to afford (±)-cis-3-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in DCM (5 mL)
  3. additionadded 2 N sodium hydroxide solution (2 mL)
  4. customthe resultant reaction mixture
  5. stirringwas stirred at room temperature for 2 h
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with DCM (5 mL)
  8. concentrationThe combined organic layer was concentrated under reduced pressure
  9. customthe residue was purified by silica gel flash column chromatography
  10. washby eluting with 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c0ae7095c18f4a41bcd36c88222a92e8
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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