Methanamine, N-methoxy-, hydrochloride (1:1) → Benzyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

HRID 453657Notes

Reaction equation

HRID 453657 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:21][NH:22][O:23][CH3:24].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:24][O:23][N:22]([CH3:21])[C:17]([CH:14]1[CH2:13][CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:16][CH2:15]1)=[O:19]

Participants

7

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 7364891-Carbobenzoxy-4-piperidinecarboxylic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 22574154Benzyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateYield 67.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(benzyloxycarbonyl)piperidine-4-carboxylic acid (10 g, 38.0 mmol), N,O-dimethylhydroxylamine hydrochloride (5.56 g, 57.0 mmol), and CH2Cl2 (120 mL) was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (10.92 g, 57.0 mmol) and 4-(dimethylamino)pyridine (0.464 g, 3.80 mmol). The mixture was cooled in an ice bath and treated with N,N-diisopropylethylamine (13.23 mL, 76 mmol) over 3 min. After 10 min, the cooling bath was removed and the mixture was stirred at RT overnight (˜14 h). The mixture was diluted with CH2Cl2 (150 mL), washed with saturated NaHCO3 (3×50 mL), 2 M HCl (2×50 mL) and brine, dried over MgSO4, and concentrated to provide a residue. The residue was purified by flash chromatography using a 120 g silica gel cartridge and 10:1 Hex/EtOAc to elute the product. The fractions containing the product were pooled and concentrated on a rotary evaporator to give the title compound (7.8 g, 25.5 mmol, 67% yield) as a pale yellow oil. LC-MS: 307.1, (M+H)+. 1H-NMR (400 MHz, CDCl3) δ ppm 7.25-7.37 (5H, m), 5.11 (2H, s), 4.21 (2H, s), 3.66-3.71 (3H, m), 3.16 (3H, s), 2.83 (3H, d, J=5.93 Hz), 1.64-1.75 (4H, m).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. customthe cooling bath was removed
  3. additionThe mixture was diluted with CH2Cl2 (150 mL)
  4. washwashed with saturated NaHCO3 (3×50 mL), 2 M HCl (2×50 mL) and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto provide a residue
  8. customThe residue was purified by flash chromatography
  9. washto elute the product
  10. additionThe fractions containing the product
  11. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-be45d5437cd14672a465dd7433dc0f7e
Source dataset
uspto-grants-2013_07
Patent number
US08492550B2

Reaction notes

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