N-Methylpiperidine → HCID 178502741, compound

HRID 271348Notes

Reaction equation

HRID 271348 reaction equation
[C:1]([O:5][C:6]([CH2:8][C@@H:9]1[CH2:12][C@H:11]([C:13]([OH:15])=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCCCC1.ClC(OCC(C)C)=O.Cl.[CH3:32][NH:33][O:34][CH3:35]>ClCCl>[C:1]([O:5][C:6](=[O:7])[CH2:8][C@H:9]1[CH2:10][C@@H:11]([C:13](=[O:15])[N:33]([O:34][CH3:35])[CH3:32])[CH2:12]1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 12291N-MethylpiperidineHCID 62365Isobutyl chloroformateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 178451083HCID 178451083, compound

Product 1

HCID 178502741HCID 178502741, compoundYield 99.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice cold solution of 1.74 g of cis-3-tert-butoxycarbonylmethyl-cyclobutanecarboxylic acid, 3 mL of N-methyl-piperidine, and 50 mL of dichloromethane was added 1.7 mL of isobutyl chloroformate drop-wise over 5 min. After an additional 5 min, 1.6 g of N-methyl-N-methoxy-amine hydrochloride was added and the mixture allowed to warm with stirring overnight. The resulting mixture was diluted with 100 mL of dichloromethane, washed with 100 mL of water, 100 mL of 0.1 N HCl, 50 mL of saturated sodium carbonate and dried over magnesium sulfate. The solution was diluted with 50 mL of toluene and concentrated under reduced pressure. Drying under vacuum overnight gave 2.08 g of product as a colorless thick oil: MS (m+1)=258.3; 1H NMR (400 MHz, CDCl3) 3.62 (s, 3H), 3.16 (s, 3H), 2.35 (d, 2H), 2.0 (dd, 1H), 1.4 (s, 9H).

Workup

  1. temperatureto warm
  2. washwashed with 100 mL of water, 100 mL of 0.1 N HCl, 50 mL of saturated sodium carbonate
  3. dry with materialdried over magnesium sulfate
  4. additionThe solution was diluted with 50 mL of toluene
  5. concentrationconcentrated under reduced pressure
  6. customDrying under vacuum overnight

Sources & evidence

ORD record
ord-07bb58247aac4a578401c1dacc1af987
Source dataset
uspto-grants-2008_11
Patent number
US07452893B2

Reaction notes

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