Dichloromethane → (S)-4-(2-chloro-8-iodo-9-methyl-9H-purin-6-yl)-3-methylmorpholine

HRID 2063362Notes

Reaction equation

HRID 2063362 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[N:3]=1.C([N-]C(C)C)(C)C.[Li+].[I:27]Cl.ClCCl>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([I:27])[N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[N:3]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 24640Iodine chlorideHCID 2724682Lithium diisopropylamideHCID 58222544(S)-4-(2-chloro-9-methyl-9H-purin-6-yl)-3-methylmorpholine

Product 1

HCID 58222526(S)-4-(2-chloro-8-iodo-9-methyl-9H-purin-6-yl)-3-methylmorpholineYield 40.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To (S)-4-(2-chloro-9-methyl-9H-purin-6-yl)-3-methylmorpholine (750.0 mg, 2.80 mmol) in anhydrous THF (16 mL) at −78° C. under N2 was added freshly prepared lithium diisopropylamide in THF (2.0 eq). The resultant wine colored reaction was stirred at −78° C. After 1 h iodine monochloride in dichloromethane (4.2 mL, 4.2 mmol, 1.0 M, 1.5 eq.) was added and stirred at RT for 16 h. The reaction mixture was quenched with saturated aqueous sodium thiosulfate. 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 solid (446.4 mg, 40.5%). 1H NMR (CDCl3, 400 MHz) δ ppm 5.28 (broad s, 2H), 3.99 (m, 1H), 3.75 (m, 2H), 3.67 (s, 3H), 3.59 (m, 1H), 3.49 (broad s, 1H), 1.38 (d, 3H); LC-MS m/z (method A)=394/396 [M+H]+, RT=1.92 min.

Workup

  1. customThe resultant wine colored reaction
  2. stirringstirred at RT for 16 h
  3. customThe reaction mixture was quenched with saturated aqueous sodium thiosulfate
  4. customVolatile solvent was then evaporated in vacuo
  5. additionthe crude was diluted with ethyl acetate
  6. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate, water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-6cc8c3f9abdc44488d89e5ff171f8d6e
Source dataset
uspto-grants-2012_10
Patent number
US08288381B2

Reaction notes

Loading…