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

HRID 1804859Notes

Reaction equation

HRID 1804859 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:18][NH:19][O:20][CH3:21].Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:21][O:20][N:19]([CH3:18])[C:14]([CH:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]1)=[O:16]

Participants

7

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateYield 90.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (9.20 g, 40.1 mmol), N,O-dimethylhydroxylamine hydrochloride (5.87 g, 60.2 mmol) and CH2Cl2 (120 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (11.54 g, 60.2 mmol), N,N-diisopropylethylamine (10.51 mL, 60.2 mmol) and 4-(dimethylamino)pyridine (250 mg, 2.046 mmol) before being stirred at RT overnight. After this time, the mixture was diluted with DCM (100 mL) and washed sequentially with 1 M hydrochloric acid (2×75 mL), saturated NaHCO3 (100 mL), and brine (100 mL). The organic phase was dried (MgSO4) and then concentrated in vacuo to give tert-butyl 4-(methoxy(methyl)carbamoyl)-piperidine-1-carboxylate as a colorless oil (9.9 g), which was used in the next step without any further purification.

Workup

  1. washwashed sequentially with 1 M hydrochloric acid (2×75 mL), saturated NaHCO3 (100 mL), and brine (100 mL)
  2. dry with materialThe organic phase was dried (MgSO4)
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-66fd2925892e4dfba52c4c9e9bc3523e
Source dataset
uspto-grants-2013_01
Patent number
US08354432B2

Reaction notes

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