Dimethylformamide → tert-butyl N-[1-(5-cyanopyridin-2-yl)pyrrolidin-3-yl]carbamate

HRID 252099Notes

Reaction equation

HRID 252099 reaction equation
[CH:1]([N:4]([CH:7]([CH3:9])C)[CH2:5][CH3:6])([CH3:3])C.ClC1C=[CH:17][C:14]([C:15]#[N:16])=[CH:13][N:12]=1.[C:19]([O:23][C:24](C1CCNC1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C[N:32](C=O)C>ClCCl>[C:19]([O:23][C:24](=[O:25])[NH:32][CH:9]1[CH2:6][CH2:5][N:4]([C:1]2[CH:3]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][N:12]=2)[CH2:7]1)([CH3:22])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 22394392tert-Butyl pyrrolidine-3-carboxylate

Product 1

HCID 66854656tert-butyl N-[1-(5-cyanopyridin-2-yl)pyrrolidin-3-yl]carbamateYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Stir a solution of diisopropylethylamine (9.5 mL, 54.3 mmol), 6-chloronicotinonitrile (5 g, 36.2 mmol) and 3-tert-butyloxycarbonylpyrrolidine (10 g, 54.3 mmol) in DMF (10 mL). After 3 days, dilute with dichloromethane and an aqueous saturated solution of sodium bicarbonate and separate the layers. Extract the aqueous layer once with dichloromethane, dry (sodium sulfate), filter and concentrate. Filter through a plug of silica gel, wash with dichloromethane and concentrate to give [1-(5-cyanopyridin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester as a white solid (8.13 g, 78%). 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, 1H, J=2.4 Hz, 1.0 Hz), 7.58-7.55 (m, 1H), 6.33 (dd, 1H, J=9.8 Hz, 1.0 Hz), 4.85-4.7 (m, 1H), 4.40-4.25 (m, 1H), 3.85-3.30 (m, 4H), 2.35-2.25 (m, 1H), 2.08-1.90 (m, 1H), 1.43 (s, 9H); MS (ES): m/z=289 [M+H]+.

Workup

  1. customan aqueous saturated solution of sodium bicarbonate and separate the layers
  2. extractionExtract the aqueous layer once with dichloromethane
  3. dry with materialdry (sodium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. filtrationFilter through a plug of silica gel
  7. washwash with dichloromethane
  8. concentrationconcentrate

Sources & evidence

ORD record
ord-572ddc8cddb546f29b39ec9472224a26
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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