1-Chloro-2-iodoethane → (S)-4-(2-chloro-9-ethyl-8-iodo-9H-purin-6-yl)-3-methylmorpholine

HRID 2063369Notes

Reaction equation

HRID 2063369 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH3:12])=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[N:3]=1.C([N-]C(C)C)(C)C.[Li+].ClCC[I:31]>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([I:31])[N:8]2[CH2:11][CH3:12])=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[N:3]=1

Participants

5

Reactant 3

HCID 1364381-Chloro-2-iodoethaneHCID 2724682Lithium diisopropylamideHCID 58222539(S)-4-(2-chloro-9-ethyl-9H-purin-6-yl)-3-methylmorpholine

Product 1

HCID 58222524(S)-4-(2-chloro-9-ethyl-8-iodo-9H-purin-6-yl)-3-methylmorpholineYield 90.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To (S)-4-(2-chloro-9-ethyl-9H-purin-6-yl)-3-methylmorpholine (465.0 mg, 1.65 mmol) in anhydrous THF (6.7 mL) at −78° C. under N2 was added freshly prepared lithium diisopropylamide in THF (2.0 eq). The reaction was stirred at −78° C. under N2 for 2 hours, and 1-chloro-2-iodoethane (1.01 g, 5.78 mmol, 3.5 eq.) was added. The reaction mixture was then stirred at RT for 3 days and then quenched with saturated aqueous sodium ammonium chloride solution at 0° C. Volatile solvent was then evaporated in vacuo, and the crude was diluted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in hexane) to give the desired compound as a foam (610.0 mg, 90.7%). 1H NMR (CDCl3, 400 MHz) δ ppm 5.28 (broad s, 2H), 4.17 (q, J=7.4 Hz, 2H), 4.00 (dd, J=11.3, 3.4 Hz, 1H), 3.75 (m, 2H), 3.59 (m, 1H), 3.48 (broad s, 1H), 1.37 (m, 6H); LC-MS m/z (method B2)=408 [M+H]+, RT=2.06 min.

Workup

  1. stirringThe reaction mixture was then stirred at RT for 3 days
  2. customquenched with saturated aqueous sodium ammonium chloride solution at 0° C
  3. customVolatile solvent was then evaporated in vacuo
  4. additionthe crude was diluted with ethyl acetate
  5. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate, water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-a0c76ebd5e8b4ef6b724ee16ea3124e8
Source dataset
uspto-grants-2012_10
Patent number
US08288381B2

Reaction notes

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