Pyrrolidine → cis-Tert-butyl 2-methyl-5-(pyrrolidine-1-carbonyl)piperidine-1-carboxylate

HRID 931324Notes

Reaction equation

HRID 931324 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1.[C:39]([O:43][C:44]([N:46]1[C@H:51]([CH3:52])[CH2:50][CH2:49][C@H:48]([C:53](O)=[O:54])[CH2:47]1)=[O:45])([CH3:42])([CH3:41])[CH3:40].C[C@H]1NC[C@@H](C(O)=O)CC1>ClCCl.O>[CH3:52][C@H:51]1[CH2:50][CH2:49][C@@H:48]([C:53]([N:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)=[O:54])[CH2:47][N:46]1[C:44]([O:43][C:39]([CH3:40])([CH3:42])[CH3:41])=[O:45]

Participants

8

Reactant 5

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58504783(3S,6R)-6-Methylpiperidine-3-carboxylic acidHCID 66739888Cis-6-Methyl-Piperidine-1,3-Dicarboxylic Acid 1-Tert-Butyl Ester

Product 1

HCID 131735166cis-Tert-butyl 2-methyl-5-(pyrrolidine-1-carbonyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′,-tetramethyluronium hexafluorophosphate (HATU) (7.50 g, 19.72 mmol), diisopropylethylamine (7.08 mL, 39.45 mmol) and pyrrolidine (1.40 g, 19.72 mmol) were added to a solution of cis-1-(tert-butoxycarbonyl)-6-methylpiperidine-3-carboxylic acid (synthesized by N-Boc protection of cis-6-methylpiperidine-3-carboxylic acid, analogously prepared by the method described in J. Med. Chem. 2011, 54, 1871-1895.) (4.0 g, 16.44 mmol) in anhydrous dichloromethane (40 mL) at room temperature. The reaction mixture was stirred at room temperature for 4 h. Water was added and the mixture was extracted with dichloromethane. The organics were dried over sodium sulfate and concentrated under reduced pressure to afford cis-tert-butyl 2-methyl-5-(pyrrolidine-1-carbonyl)piperidine-1-carboxylate (4.0 g). The material was used without further purification.

Workup

  1. customanalogously prepared by the method
  2. customat room temperature
  3. extractionthe mixture was extracted with dichloromethane
  4. dry with materialThe organics were dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c934e652854d4bc38da1eb8efc767da2
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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