Triethylamine → (R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate

HRID 2039875Notes

Reaction equation

HRID 2039875 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17](N1C=CN=C1)(N1C=CN=C1)=[O:18].C([N:31]([CH2:34]C)CC)C>C1COCC1>[CH3:17][O:18][N:31]([CH3:34])[C:14]([C@@H:10]1[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1)=[O:16]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 6435161-(1,1-Dimethylethyl) (3R)-1,3-piperidinedicarboxylate

Product 1

HCID 30025965(R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of (R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (233 g, 1.2 mol) in THF (1.2 L) was added carbonyldiimidazole (230 g, 1.42 mol). The mixture was stirred for 1 h under ice-water bath. A suspension of triethylamine (207 mL, 1.41 mol) and N, O-dimethylhydroxylamine hydrochloride (138 g, 1.42 mol) in THF (900 mL) was added. The reaction mixture was allowed to warm to room temperature and stirred overnight. TLC showed the reaction was complete. The solvent was evaporated, and the residue was dissolved in CH2Cl2 (1.2 L) and washed successively with 0.5 N hydrochloride solution, saturated solution of sodium carbonate and brine, dried over anhydrous sodium sulfate and evaporated to give crude compound (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (250 g, 91%), which was used in the next step directly without purification. 1H NMR (400 MHz, CDCl3): 4.05-4.19 (m, 2H), 3.72 (s, 3H), 3.17 (s, 3H), 2.75-2.85 (m, 2H), 2.65 (t, 1H), 1.90 (d, 1H), 1.60-1.78 (m, 2H), 1.44 (s, 9H).

Workup

  1. additionwas added
  2. stirringstirred overnight
  3. customThe solvent was evaporated
  4. dissolutionthe residue was dissolved in CH2Cl2 (1.2 L)
  5. washwashed successively with 0.5 N hydrochloride solution, saturated solution of sodium carbonate and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated

Sources & evidence

ORD record
ord-8f353dad03d74d9e8c1f7225909cdd12
Source dataset
uspto-grants-2013_11
Patent number
US08580823B2

Reaction notes

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