Hydrochloric Acid → Ethyl 4-(diphenylmethoxy)piperidine carboxylate

HRID 2250414Notes

Reaction equation

HRID 2250414 reaction equation
[C:1]1([CH:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12](C)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.Cl[C:24]([O:26][CH2:27][CH3:28])=[O:25]>C1(C)C=CC=CC=1>[C:16]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:11][CH2:10]2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3103DiphenylpyralineHCID 10928Ethyl chloroformate2×

Product 1

HCID 10020094Ethyl 4-(diphenylmethoxy)piperidine carboxylateYield 72%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
104 °C

Procedure

4-(Diphenylmethoxy)-1-(methyl)piperidine (prepared by neutralization of the commercial HCl salt; 4 g, 14.2 mmol, 1 equiv.) in anhydrous toluene (20 mL) was stirred at room temperature under nitrogen. Ethyl chloroformate (4.66 g, 43 mmol, 4.1 mL, 3 equiv.) was added dropwise over 5 minutes, whereupon significant effervescence was noted. The mixture was heated over the course of 1 h to reflux with an oil bath (bath temperature 104° C.). The mixture was then cooled to room temperature, whereupon more ethyl chloroformate (4 mL) was added. The mixture was heated at reflux (bath T=104° C.) for 7 h and again cooled to room temperature. The cooled mixture was concentrated and the residue purified by dry column chromatography (4×8.5 cm silica bed; 2:1 heptane:ethyl acetate) to yield 3.49 g (72%) of 4a as a slightly yellow oil. 1H NMR was consistent with the structure.

Workup

  1. temperatureThe mixture was heated over the course of 1 h
  2. additionwas added
  3. temperatureThe mixture was heated
  4. temperatureat reflux (bath T=104° C.) for 7 h
  5. temperatureagain cooled to room temperature
  6. concentrationThe cooled mixture was concentrated
  7. customthe residue purified
  8. dry with materialby dry column chromatography (4×8.5 cm silica bed; 2:1 heptane:ethyl acetate)

Sources & evidence

ORD record
ord-7335b806c12b4d27862b7e2bb67b1aac
Source dataset
uspto-grants-2008_01
Patent number
US07317026B2

Reaction notes

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