N,N,N',N'-Tetramethylethylenediamine → (6-Methoxy-4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester

HRID 1506024Notes

Reaction equation

HRID 1506024 reaction equation
C([Li])CCC.[C:6]([O:10][C:11](=[O:21])[NH:12][C:13]1[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=1)([CH3:9])([CH3:8])[CH3:7].CN(C)CCN(C)C.ClCC[I:33]>C(OCC)C>[C:6]([O:10][C:11](=[O:21])[NH:12][C:13]1[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][C:18]=1[I:33])([CH3:9])([CH3:8])[CH3:7]

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 1364381-Chloro-2-iodoethaneHCID 2763103tert-Butyl (6-methoxypyridin-3-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 58266614(6-Methoxy-4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (2.5M in hexanes, 100 mL, 240 mmol) was added dropwise over 1 h to a cooled (−78° C.) mixture of tert-butyl-6-methoxypyridin-3-ylcarbamate (16 g, 71 mmol) and N,N,N′,N′-tetramethylethylenediamine (34 mL, 221 mmol) in diethyl ether (100 mL). The reaction was stirred at −78° C. for 30 minutes, then warmed to −20° C. and left stirring for 3 h. The reaction mixture was transferred via cannula over fifteen minutes to a cold (−78° C.) solution of 1-chloro-2-iodoethane (48 g, 243 mmol) in diethyl ether (50 mL). On complete addition, the reaction mixture was allowed to warm to room temperature and left stirring at this temperature for 16 h. The reaction was quenched with saturated aqueous ammonium chloride (30 mL) and water (200 mL) then extracted with ethyl acetate (2×100 mL). The combined organic layer was washed with saturated sodium sulfite (50 mL), 1N hydrochloric acid (100 mL), water (100 mL), saturated sodium bicarbonate solution (100 mL) and brine (50 mL), dried over sodium sulfate, and evaporated to give a residue which was purified by flash chromatography (silica, 120 g column, ISCO, 0-40% ethyl acetate in hexanes) to afford the title compound as a white cyrstaline solid (18 g, 72%).

Workup

  1. temperaturea cooled
  2. temperaturewarmed to −20° C.
  3. waitleft
  4. stirringstirring for 3 h
  5. additionOn complete addition
  6. temperatureto warm to room temperature
  7. waitleft
  8. stirringstirring at this temperature for 16 h
  9. customThe reaction was quenched with saturated aqueous ammonium chloride (30 mL) and water (200 mL)
  10. extractionthen extracted with ethyl acetate (2×100 mL)
  11. washThe combined organic layer was washed with saturated sodium sulfite (50 mL), 1N hydrochloric acid (100 mL), water (100 mL), saturated sodium bicarbonate solution (100 mL) and brine (50 mL)
  12. dry with materialdried over sodium sulfate
  13. customevaporated
  14. customto give a residue which
  15. customwas purified by flash chromatography (silica, 120 g column, ISCO, 0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5165e5c0e1bb4f4b895cf7f03248ee78
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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