Hydrochloric Acid → HCID 136050798, compound

HRID 412274Notes

Reaction equation

HRID 412274 reaction equation
[NH2:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6]([CH:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)[CH:5]=[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[OH:29])[N:3]=1.Cl.[C:31]([BH3-])#N.[Na+].C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>O1CCOCC1.CCOCC.CO>[NH2:1][C:2]1[C:7]([CH2:8][O:9][CH3:31])=[C:6]([CH:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)[CH:5]=[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[OH:29])[N:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 5003444Sodium cyanoborohydrideHCID 136050723HCID 136050723, compound

Product 1

HCID 136050798HCID 136050798, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of tert-butyl 3-[2-amino-3-formyl-6-(2-hydroxyphenyl)-4-pyridinyl]-1-piperidinecarboxylate (0.100 g, 0.252 mmol) in 1,4-dioxane (2.0 mL) under an argon atmosphere was added a HCl solution of 1,4-dioxane (4N, 2.0 mL), and the stirring was continued at room temperature for 1 hr. The mixture was diluted with Et2O, and the supernatant was decanted. The precipitates were washed twice with Et2O, and dried under reduced pressure to give a pale yellow solid, which was then dissolved in methanol (2.0 mL). The mixture was allowed to cool with ice-water bath. Then sodium cyanoborohydride (0.047 g, 0.76 mmol) was added to the mixture under an argon atmosphere. The mixture was allowed to warm to room temperature, and the stirring was continued overnight. The resulting mixture was concentrated under reduced pressure. The residue was dissolved in a mixture of methylene chloride (2.0 mL) and THF (2.0 mL). To the mixture was added triethylamine (0.140 mL, 1.006 mmol) followed by di-tert-butyl dicarbonate (0.110 g, 0.503 mmol), and the stirring was continued for 2 hrs. The resulting mixture was partitioned between ethyl acetate and water. The separated organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate, 2:1) to give tert-Butyl 3-[2-amino-6-(2-hydroxyphenyl)-3-(methoxymethyl)-4-pyridinyl]-1-piperidinecarboxylate. (0.033 g, yield; 47%)

Workup

  1. customthe supernatant was decanted
  2. washThe precipitates were washed twice with Et2O
  3. customdried under reduced pressure
  4. customto give a pale yellow solid, which
  5. temperatureto cool with ice-water bath
  6. waitthe stirring was continued overnight
  7. concentrationThe resulting mixture was concentrated under reduced pressure
  8. dissolutionThe residue was dissolved in a mixture of methylene chloride (2.0 mL) and THF (2.0 mL)
  9. waitthe stirring was continued for 2 hrs
  10. customThe resulting mixture was partitioned between ethyl acetate and water
  11. washThe separated organic phase was washed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by column chromatography on silica gel (hexane:ethyl acetate, 2:1)

Sources & evidence

ORD record
ord-cabe671a30914ce7a9baff329ec95c5f
Source dataset
uspto-grants-2003_05
Patent number
US06562811B1

Reaction notes

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