Lithium iodide → (R)-4-(2-chloro-6-(iodomethyl)pyrimidin-4-yl)-3-methylmorpholine

HRID 1465839Notes

Reaction equation

HRID 1465839 reaction equation
[I-:1].[Li+].CS(O[CH2:8][C:9]1[CH:14]=[C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][C@H:16]2[CH3:21])[N:12]=[C:11]([Cl:22])[N:10]=1)(=O)=O>O1CCOCC1>[Cl:22][C:11]1[N:12]=[C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][C@H:16]2[CH3:21])[CH:14]=[C:9]([CH2:8][I:1])[N:10]=1

Participants

4

Reactant 2

HCID 66321Lithium iodideHCID 86651636(R)-(2-chloro-6-(3-methylmorpholino)pyrimidin-4-yl)methyl methanesulfonate

Product 1

HCID 71584551(R)-4-(2-chloro-6-(iodomethyl)pyrimidin-4-yl)-3-methylmorpholineYield 66%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Lithium iodide (17.57 g, 131.27 mmol) was added to (R)-(2-chloro-6-(3-methylmorpholino)pyrimidin-4-yl)methyl methanesulfonate (19.2 g, 59.67 mmol) in dioxane (300 ml) and heated to 100° C. for 2 hours under nitrogen. The reaction mixture was quenched with water (200 ml) and extracted with EtOAc (3×200 ml). The organic layers were combined and washed with 2M sodium bisulfite solution (400 ml), water (400 ml), brine (400 ml) dried over MgSO4 and then evaporated. The residue was triturated with Et2O to afford (R)-4-(2-chloro-6-(iodomethyl)pyrimidin-4-yl)-3-methylmorpholine (13.89 g, 66%); 1H NMR (400 MHz, CDCl3) 1.32 (3H, d), 3.28 (1H, td), 3.54 (1H, td), 3.69 (1H, dd), 3.78 (1H, d), 3.98-4.02 (2H, m), 4.21 (2H, s), 4.29 (1H, br s), 6.41 (1H, s); m/z: (ESI+) MH+, 354.31.

Workup

  1. customThe reaction mixture was quenched with water (200 ml)
  2. extractionextracted with EtOAc (3×200 ml)
  3. washwashed with 2M sodium bisulfite solution (400 ml), water (400 ml), brine (400 ml)
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe residue was triturated with Et2O

Sources & evidence

ORD record
ord-779c2140ade7478b86ddcae4ce713995
Source dataset
uspto-grants-2015_04
Patent number
US08999997B2

Reaction notes

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