1,2-Dichloroethane → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

HRID 579557Notes

Reaction equation

HRID 579557 reaction equation
C(Cl)CCl.[N:5]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9][CH:8]([C:11]([O-:13])=O)[CH2:7][CH2:6]1.Cl.[CH3:22][NH:23][O:24][CH3:25].C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl.O>[C:17]([O:16][C:14]([N:5]1[CH2:6][CH2:7][CH:8]([C:11](=[O:13])[N:23]([O:24][CH3:25])[CH3:22])[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 6921829HCID 6921829, compound

Product 1

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateYield 85%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

EDC (6.29 g, 32.8 mmol) was added in several portions to a stirring solution of piperidine-1,4-dicarboxylic acid, mono tert-butyl ester (5.0 g, 21.8 mmol), DMAP (10 mg), and N,O-dimethylhydroxylamine hydrochloride (3.21 g, 32.8 mmol) in dichloromethane (100 mL). To the resultant solution was added dropwise triethylamine (9.4 mL, 65.6 mmol), and the reaction mixture was stirred at room temperature overnight. The next day, the reaction mixture was poured into water, and the aqueous layer was extracted using ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give a colorless oil. Purification by column chromatography (silica gel, 0-40% ethyl acetate in heptane) gave tert-butyl-4-[methoxy(methyl)-carbamoyl]-piperidine-1-carboxylate (5.04 g, 85%) as a colorless oil; 1H NMR (CDCl3, 300 MHz) δ 4.16 (m, 2H), 3.70 (s, 3H), 3.17 (s, 3H), 2.72-2.86 (m, 3H), 1.62-1.75 (m, 4H) and 1.44 (s, 9H).

Workup

  1. extractionthe aqueous layer was extracted
  2. washThe combined organic phase was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a colorless oil
  7. customPurification by column chromatography (silica gel, 0-40% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-0083d25924fd49899a9f4edfe5e8439c
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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