N-Methylpiperidine → HCID 18758347, compound

HRID 1661745Notes

Reaction equation

HRID 1661745 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]([O:17][C:18]([NH:20][CH:21]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[C:28]([O:34][CH2:35][CH3:36])[CH:27]=1)[CH2:22][C:23]([OH:25])=O)=[O:19])([CH3:16])([CH3:15])[CH3:14].Cl.[CH3:38][NH:39][O:40][CH3:41].CN1CCCCC1>C(Cl)Cl>[C:13]([O:17][C:18]([NH:20][CH:21]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[C:28]([O:34][CH2:35][CH3:36])[CH:27]=1)[CH2:22][C:23]([N:39]([O:40][CH3:41])[CH3:38])=[O:25])=[O:19])([CH3:14])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 12291N-MethylpiperidineHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 18758348HCID 18758348, compound

Product 1

HCID 18758347HCID 18758347, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of carbonyldiimidazole (0.96 g, 5.9 mmol), 3-(tert-butoxycarbonylamino)-3-(3-ethoxy-4-methoxyphenyl)propionic acid (2.0 g, 5.9 mmol) and methylene chloride (25 mL) was stirred at room temperature for 1 hr and then cooled to 5° C. A solution of N,O-dimethylhydroxyamine hydrochloride (0.86 g, 8.85 mmol) and 1-methylpiperidine (0.87 g, 8.85 mmol) in methylene chloride (10 mL) was added slowly. The mixture was stirred at room temperature for 1 hr and then quenched with water (20 mL). The organic layer was separated and then was washed with 1N citric acid, water, and brine. The organic layer was dried and concentrated in vacuo to give an oil. This oil was purified by chromatography (silica gel, methylene chloride:ethyl acetate 8:2) to afford 3-(tert-butyloxycarbonylamino)-3-(3-ethoxy-4-methoxyphenyl)-N-methoxy-N-methylpropanamide as a white solid (1.76 g, 78%); 1H NMR (CDCl3) δ 6.86-6.78 (m, 3H), 6.07 (b, 1H), 5.01 (m, 1H), 4.10 (q, J=6.9 Hz, 2H), 3.84 (s, 3H), 3.50 (s, 3H), 3.10 (s, 3H), 3.02 (m, 2H), 2.84-2.75 (dd, J=5.3 and 15.2 Hz, 1H), 1.45 (t, J=7.1 Hz, 3H), 1.41 (s, 9H); 13C NMR (CDCl3) δ 171.81, 155.18, 148.39, 148.19, 134.82, 118.12, 111.41, 111.18, 79.27, 64.26, 61.19, 55.90, 51.25, 37.80, 31.87, 28.33, 14.73.

Workup

  1. temperaturecooled to 5° C
  2. stirringThe mixture was stirred at room temperature for 1 hr
  3. customquenched with water (20 mL)
  4. customThe organic layer was separated
  5. washwas washed with 1N citric acid, water, and brine
  6. customThe organic layer was dried
  7. concentrationconcentrated in vacuo
  8. customto give an oil
  9. customThis oil was purified by chromatography (silica gel, methylene chloride:ethyl acetate 8:2)

Sources & evidence

ORD record
ord-97f6d17abea549d0bb94912a897bf6ac
Source dataset
uspto-grants-2011_10
Patent number
US08030343B2

Reaction notes

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