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

HRID 451648Notes

Reaction equation

HRID 451648 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(N1C=CN=C1)(N1C=CN=C1)=O.C(N(CC)CC)C.Cl.[CH3:37][NH:38][O:39][CH3:40]>C1COCC1>[CH3:40][O:39][N:38]([CH3:37])[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

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 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 in an 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 rt and stirred overnight. After tlc showed the reaction was complete, the solvent was evaporated. The residue was dissolved in CH2Cl2 (1.2 L) and washed successively with 0.5 N aq HCl, satd aq Na2CO3 and brine, dried over anhydrous sodium sulfate and evaporated to give (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): 1.44 (s, 9H), 1.60-1.78 (m, 2H), 1.90 (m, 1H), 2.65 (m, 1H), 2.75-2.85 (m, 2H), 3.16 (s, 3H), 3.71 (s, 3H), 4.05-4.19 (m, 2H). MS (E/Z): 273 (M+H+).

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 aq HCl
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated

Sources & evidence

ORD record
ord-4a07c56afc04468b9dd8f0d8f42af4ec
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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