Triethylamine → cis-Tert-butyl 3-(dimethylcarbamoyl)-4-methylpiperidine-1-carboxylate

HRID 931273Notes

Reaction equation

HRID 931273 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([CH3:14])[C@H:10]([C:15]([OH:17])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[C@H]1C[CH2:23][NH:22][CH2:21][C@H]1C(O)=O.C(N(CC)CC)C.Cl.CNC.C(N1C=CN=C1)(N1C=CN=C1)=O>O1CCCC1>[CH3:21][N:22]([CH3:23])[C:15]([C@H:10]1[C@@H:11]([CH3:14])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9]1)=[O:17]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 682631,1'-CarbonyldiimidazoleHCID 86317483(3S,4S)-1-Boc-4-methyl-piperidine-3-carboxylic acidHCID 92975855rac-(3R,4R)-4-methylpiperidine-3-carboxylic acid

Product 1

HCID 131735161cis-Tert-butyl 3-(dimethylcarbamoyl)-4-methylpiperidine-1-carboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of cis-1-(tert-butoxycarbonyl)-4-methylpiperidine-3-carboxylic acid (prepared by N-Boc protection of cis-4-methylpiperidine-3-carboxylic acid, synthesized by the method described in Bulletin de la Societe Chimique de France 1986, 4, 663-8.) (0.4 g, 1.64 mmol) in tetrahydrofuran were added triethylamine (0.2 mL, 1.64 mmol), dimethylamine hydrochloride (132 mg, 1.64 mmol), and 1,1′-carbonyldiimidazole (CDI, 265 mg, 1.64 mmol). After 2 h, the mixture was quenched with water and the aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford cis-tert-butyl 3-(dimethylcarbamoyl)-4-methylpiperidine-1-carboxylate (0.3 g, 68%) as a yellow solid. The material was used without further purification.

Workup

  1. customsynthesized by the method
  2. customthe mixture was quenched with water
  3. extractionthe aqueous layer was extracted with ethyl acetate (2×10 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-dd618ea681a84ef8a58f7bf638c71c2a
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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