Trimethyl phosphite → dimethyl (2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylphosphonate

HRID 1923212Notes

Reaction equation

HRID 1923212 reaction equation
Br[CH2:2][C:3]1[N:4]([CH3:19])[C:5]2[C:10]([N:11]=1)=[C:9]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[N:8]=[C:7]([Cl:18])[N:6]=2.[CH3:20][O:21][P:22]([O:25]C)[O:23][CH3:24]>>[Cl:18][C:7]1[N:6]=[C:5]2[C:10]([N:11]=[C:3]([CH2:2][P:22](=[O:25])([O:23][CH3:24])[O:21][CH3:20])[N:4]2[CH3:19])=[C:9]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:8]=1

Participants

3

Reactant 2

HCID 8472Trimethyl phosphiteHCID 596034814-(8-(bromomethyl)-2-chloro-9-methyl-9H-purin-6-yl)morpholine

Product 1

HCID 59605250dimethyl (2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylphosphonateYield 76.5%

Procedure

A mixture of 4-(8-(bromomethyl)-2-chloro-9-methyl-9H-purin-6-yl)morpholine (0.25 g, 0.72 mmol) and trimethylphosphite (4.0 mL, 34 mmol) was stirred at 120 degree for 1.25 hours. The resulting suspension was partitioned between water and dichloromethane. The aqueous layer was neutralized and extracted again with dichloromethane. The organic extracts were washed with water, dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography (0-5% methanol in DCM) to give the title compound (207 mg, 76%).

Workup

  1. customThe resulting suspension was partitioned between water and dichloromethane
  2. extractionextracted again with dichloromethane
  3. washThe organic extracts were washed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (0-5% methanol in DCM)

Sources & evidence

ORD record
ord-91920901c8284a5b97e6be3e7606aaee
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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