Hydrochloric Acid → HCID 59865002, compound

HRID 1669744Notes

Reaction equation

HRID 1669744 reaction equation
CC([CH:5]1[CH2:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][CH2:25][C:24]([CH3:29])([CH3:28])[CH2:23]3)=[CH:14][CH:13]=2)(O)[CH2:8][CH2:7][N:6]1C([O-])=O)(C)C.Cl>C(O)C>[CH3:28][C:24]1([CH3:29])[CH2:25][CH2:26][CH2:27][N:22]([CH2:21][CH2:20][CH2:19][O:18][C:15]2[CH:14]=[CH:13][C:12]([C:9]3[CH2:10][CH2:5][NH:6][CH2:7][CH:8]=3)=[CH:17][CH:16]=2)[CH2:23]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86625602HCID 86625602, compound

Product 1

HCID 59865002HCID 59865002, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
7.5 °C

Procedure

A mixture of crude 1,1-dimethylethyl-4-(4-{[3-(3,3-dimethyl-1-piperidinyl)propyl]oxy}phenyl)-4-hydroxy-1-piperidinecarboxylate (100 g) in 95% ethanol (500 ml) is cooled to 5-10° C. and concentrated hydrogen chloride (300 ml) is added at 5-10° C. over about 45 min, then stirred for about 15 min. The mixture is then heated to reflux (about 80-85° C.) for about 6 h. The mixture is concentrated under vacuum at 50-60° C., then water (500 ml) is added. The mixture is then cooled to 5-10° C. and the pH adjusted to pH 10-12 with 2N sodium hydroxide solution at 5-10° C. The mixture is warmed to 25-35° C., and extracted with ethyl acetate (500 ml, then 2×200 ml). The combined ethyl acetate layers are washed with water (200 ml), then 10% aqueous sodium chloride solution (200 ml). The solvent is removed under vacuum and the product is purified by column chromatography (100-200 mesh silica gels) using a linear gradient of MeOH/DCM 0-70% to give the title compound (21.7 g).

Workup

  1. temperatureThe mixture is then heated
  2. temperatureto reflux (about 80-85° C.) for about 6 h
  3. concentrationThe mixture is concentrated under vacuum at 50-60° C.
  4. additionwater (500 ml) is added
  5. temperatureThe mixture is then cooled to 5-10° C.
  6. customadjusted to pH 10-12 with 2N sodium hydroxide solution at 5-10° C
  7. temperatureThe mixture is warmed to 25-35° C.
  8. extractionextracted with ethyl acetate (500 ml
  9. washThe combined ethyl acetate layers are washed with water (200 ml)
  10. customThe solvent is removed under vacuum
  11. customthe product is purified by column chromatography (100-200 mesh silica gels)

Sources & evidence

ORD record
ord-12829ad670214256ac4458555bd64b28
Source dataset
uspto-grants-2011_08
Patent number
US07989629B2

Reaction notes

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