Selectfluor → Tert-butyl 1-(5'-chloro-3'-fluoro-3,5-dimethyl-2,4'-bipyridin-2'-yl)piperidin-4-ylcarbamate

HRID 2172883Notes

Reaction equation

HRID 2172883 reaction equation
[Cl:1][C:2]1[C:3]([C:22]2[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][N:23]=2)=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[B-](F)(F)(F)[F:31].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(#N)C>[Cl:1][C:2]1[C:3]([C:22]2[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][N:23]=2)=[C:4]([F:31])[C:5]([N:8]2[CH2:9][CH2:10][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:19])[CH3:20])[CH2:12][CH2:13]2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 2724933SelectfluorHCID 69043856Tert-butyl (1-(5'-chloro-3,5-dimethyl-[2,4'-bipyridin]-2'-yl)piperidin-4-yl)carbamate

Product 1

HCID 86691910Tert-butyl 1-(5'-chloro-3'-fluoro-3,5-dimethyl-2,4'-bipyridin-2'-yl)piperidin-4-ylcarbamateYield 29%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A cooled (0° C.), stirred suspension of tert-butyl (1-(5′-chloro-3,5-dimethyl-[2,4′-bipyridin]-2′-yl)piperidin-4-yl)carbamate (550 mg, 1.32 mmol) in acetonitrile (13 mL) was treated with Selectfluor® (827 mg, 2.24 mmol) portionwise. A light yellow solution was obtained and stirring was continued for 2 h. LC-MS showed the reaction was ˜70% complete. The reaction was quenched with water at this point to avoid more by-product formation. EtOAc was added and layers were separated. The aqueous layer was extracted with EtOAc (2×). The organic extract was dried over sodium sulfate and concentrated to give the crude product, which was purified on ISCO separation system with a 12-gram column using 0-40% EtOAc in heptane to afford 164 mg (29%) of white foam: LRMS (M+H)+: 435.1; 1H NMR (400 MHz, CDCl3) δ 1.43-1.50 (m, 11 H), 2.03 (d, J=12.13 Hz, 2 H), 2.14 (s, 3 H), 2.39 (s, 3 H), 2.90-3.12 (m, 2 H), 3.69 (br. s., 1 H), 3.87-4.08 (m, 2 H), 4.48 (br. s., 1 H), 7.46 (s, 1 H), 8.09 (s, 1 H), 8.40 (s, 1 H).

Workup

  1. customA light yellow solution was obtained
  2. stirringstirring
  3. customThe reaction was quenched with water at this point
  4. additionEtOAc was added
  5. customlayers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×)
  7. extractionThe organic extract
  8. dry with materialwas dried over sodium sulfate
  9. concentrationconcentrated
  10. customto give the crude product, which
  11. customwas purified on ISCO separation system with a 12-gram column

Sources & evidence

ORD record
ord-d289286558e642d2949436e0a3bbf7ac
Source dataset
uspto-grants-2015_06
Patent number
US09056865B2

Reaction notes

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