Ethyl (diethoxyphosphoryl)methanesulfonate → Ethyl 2-[(3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]ethenesulfonate

HRID 552707Notes

Reaction equation

HRID 552707 reaction equation
[CH2:1]([O:3][S:4]([CH2:7]P(OCC)(OCC)=O)(=[O:6])=[O:5])[CH3:2].C([Li])CCC.[Cl:21][C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[N:24]=[CH:25][N:26]2[CH:31]1[CH:35]2[O:36][C:37]([CH3:40])([CH3:39])[O:38][CH:34]2[CH:33]([CH:41]=O)[O:32]1>C1COCC1.CCCCCC>[Cl:21][C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[N:24]=[CH:25][N:26]2[C@H:31]1[C@@H:35]2[O:36][C:37]([CH3:40])([CH3:39])[O:38][C@@H:34]2[C@@H:33]([CH:41]=[CH:7][S:4]([O:3][CH2:1][CH3:2])(=[O:5])=[O:6])[O:32]1

Participants

6

Reactant 3

HCID 10934205Ethyl (diethoxyphosphoryl)methanesulfonateHCID 222194356-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 86607308Ethyl 2-[(3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]ethenesulfonateYield 81%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of (diethoxy-phosphoryl)-methanesulfonic acid ethyl ester (7.991 g, 0.03070 mol) in THF (100 mL), at −78° C. under an atmosphere of nitrogen, was added dropwise 2.5M n-butyllithium in hexane (13 mL), and the solution was stirred for 30 minutes. Freshly prepared 6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]-dioxole-4-carbaldehyde (13.10 g, 0.03026 mol) in THF (100 mL) was added over 15 min at −78° C. The reaction was allowed to slowly warm to −10° C. over 4 hours with stirring. The reaction was quenched with water (400 mL) and 5M ammonium chloride in water (100 mL) and extracted with methylene chloride (600 mL). The organic phase was concentrated in vacuo and the residue was purified by flash chromatography (30 to 100% EtOAc:hexanes) to yield the product as a foam (10.5 g, 81%).

Workup

  1. stirringwith stirring
  2. customThe reaction was quenched with water (400 mL) and 5M ammonium chloride in water (100 mL)
  3. extractionextracted with methylene chloride (600 mL)
  4. concentrationThe organic phase was concentrated in vacuo
  5. customthe residue was purified by flash chromatography (30 to 100% EtOAc:hexanes)

Sources & evidence

ORD record
ord-d810f7f131da4bf3a4cf09580c413cf8
Source dataset
uspto-grants-2011_05
Patent number
US07951810B2

Reaction notes

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