Pyridine → Tert-butyl 2-(fluorocarbonyl)pyrrolidine-1-carboxylate

HRID 592122Notes

Reaction equation

HRID 592122 reaction equation
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10](O)=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1C=CC=CC=1.N1C(F)=NC(F)=NC=1[F:24]>C(Cl)Cl>[F:24][C:10]([CH:9]1[CH2:13][CH2:14][CH2:15][N:8]1[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])=[O:11]

Participants

5

Reactant 3

HCID 1049PyridineHCID 12664Cyanuric fluorideHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-

Product 1

HCID 14824272Tert-butyl 2-(fluorocarbonyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Boc-L-Proline (4.5 g, 0.02 mmol) and pyridine (8.45 mL, 0.104 mmol) in DCM (20 mL) cooled in an ice bath was added dropwise cyanuric fluoride (5.35 mL, 0.0627 mmol). After the addition the reaction became milky. The solution was stirred at 0° C. for 10 min then warmed to RT and stirred for 4 h. The reaction was quenched with water, and thrice extracted with DCM. The combined organic extracts were washed with brine, dried, and concentrated in vacuo to afford tert-butyl 2-(fluorocarbonyl)pyrrolidine-1-carboxylate. The crude acid fluoride was used in next coupling reaction immediately.

Workup

  1. additionAfter the addition the reaction
  2. temperaturethen warmed to RT
  3. stirringstirred for 4 h
  4. customThe reaction was quenched with water, and thrice
  5. extractionextracted with DCM
  6. washThe combined organic extracts were washed with brine
  7. customdried
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8bccb25686134ef99cd0d0f9f06a9e48
Source dataset
uspto-grants-2016_01
Patent number
US09238675B2

Reaction notes

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