Iodine → tert-Butyl (4-chloro-3-iodopyridin-2-yl)carbamate

HRID 1615895Notes

Reaction equation

HRID 1615895 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:3]=1.CN(CCN(C)C)C.[Li]CCCC.[I:29]I.S([O-])(O)=O.[Na+]>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[C:3]=1[I:29]

Participants

8

Reactant 5

HCID 807IodineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 1516418tert-butyl N-(4-chloropyridin-2-yl)carbamateHCID 23665763Sodium BisulfiteHCID 178418339Butyllithium

Product 1

HCID 59852886tert-Butyl (4-chloro-3-iodopyridin-2-yl)carbamateYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a 250 mL round bottom flask was charged with tert-butyl (4-chloropyridin-2-yl)carbamate (5 g, 21.87 mmol) and dissolved in THF (109 mL). The stirring solution was placed in a dry ice bath and cooled to −78° C. TMEDA (8.25 mL, 54.7 mmol) was then added and the flask was flushed with nitrogen. 2.5M n-BuLi in hexanes (21.87 mL, 54.7 mmol) was then added over a period of 30 min. The mixture was stirred at −78° C. for 1 h then treated drop wise with a solution of iodine (13.87 g, 54.7 mmol) in anhydrous THF (16 mL) at −78° C. After the addition was complete, the reaction was stirred at −78° C. for 30 min then allowed to warm to rt. The mixture was treated with a solution of sodium hydrogen sulfite (16 g) in H2O (100 mL) and stirred for 30 min then extracted with EtOAc. The extract was washed with brine, dried (MgSO4) and concentrated in vacuo. The product was purified by flash chromatography: (90 g, equilibrated with DCM, loaded with DCM, initial waste: 0 mL, fraction size: 27 mL 18×150 mm, and eluted with MeOH in dichloromethane 0% [180 mL], 0-5% [360 mL], 5% [700 mL]). Collected fractions to give tert-butyl (4-chloro-3-iodopyridin-2-yl)carbamate (6.59 g, 85% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.28 (d, J=5.0 Hz, 1H), 7.43 (br. s., 1H), 7.10 (d, J=5.0 Hz, 1H), 1.56 (s, 9H)

Workup

  1. customThe stirring solution was placed in a dry ice bath
  2. customthe flask was flushed with nitrogen
  3. additionAfter the addition
  4. stirringthe reaction was stirred at −78° C. for 30 min
  5. temperatureto warm to rt
  6. stirringstirred for 30 min
  7. extractionthen extracted with EtOAc
  8. washThe extract was washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customThe product was purified by flash chromatography
  12. washinitial waste: 0 mL, fraction size: 27 mL 18×150 mm, and eluted with MeOH in dichloromethane 0% [180 mL], 0-5% [360 mL], 5% [700 mL])

Sources & evidence

ORD record
ord-149b32f322c840739b8b5b6b845fc8a0
Source dataset
uspto-grants-2014_07
Patent number
US08765767B2

Reaction notes

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