Phosphate → HCID 10020128, compound

HRID 1482386Notes

Reaction equation

HRID 1482386 reaction equation
COC1C=CC(C(C2C=CC(OC)=CC=2)(C2C=CC=CC=2)[O:10][CH2:11][C@H:12]2[O:16][C@@H:15]([N:17]3[CH:22]=[C:21]([CH3:23])[C:20](=[O:24])[NH:19][C:18]3=[O:25])[CH2:14][C@@H:13]2[OH:26])=CC=1.[C:41](O)(=[O:47])[CH2:42][CH2:43][C:44]([CH3:46])=[O:45].Cl.C(N=C=NCCCN(C)C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.P([O-])([O-])([O-])=O>CN(C1C=CN=CC=1)C.ClCCl.ClCCl.C(O)C.CO>[O:45]=[C:44]([CH3:46])[CH2:43][CH2:42][C:41]([O:26][C@H:13]1[CH2:14][C@H:15]([N:17]2[CH:22]=[C:21]([CH3:23])[C:20](=[O:24])[NH:19][C:18]2=[O:25])[O:16][C@@H:12]1[CH2:11][OH:10])=[O:47]

Participants

10

Reactant 5

HCID 1061PhosphateHCID 6101p-Toluenesulfonic acidHCID 11579Levulinic AcidHCID 1624195'-O-(4,4'-Dimethoxytrityl)thymidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 10020128HCID 10020128, compoundYield 93%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 21584144Dichloromethane ethanolSolvent

Procedure

1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione (Compound SP761) (1.09 g, 2 mmol), levulinic acid (0.29 ml, 2.8 mmol), N,N-dimethyl-4-aminopyridine (DMAP) (73 mg, 0.6 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl, 538 mg, 2.8 mmol) were dissolved in dichloromethane (2 ml) under a nitrogen atmosphere, and the mixture was stirred at room temperature for 15 minutes. 0.6 ml of methanol was added to the reaction solution, then p-toluenesulfonic acid (532 mg, 2.8 mmol) was added and the mixture was stirred at room temperature for 1 minute. 3 ml of phosphate buffer (pH=6, 1 M) was added to the above reaction solution, and the mixture was stirred for 2 minutes. 10 ml of a dichloromethane/ethanol solution (5:1) was added to the reaction solution, and the mixture was separated by 7 ml of phosphate buffer (pH=6, 1 M). The organic layer was collected, the aqueous layer was separated by 15 ml of a dichloromethane/ethanol solution (5:1) twice, and the organic layers were collected. The collected organic layers were combined, and sodium sulfate was added for drying. Sodium sulfate was then removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=65:35→100:0) to afford the desired compound (Compound SP762) (632.5 mg, 93%).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 minute
  2. stirringthe mixture was stirred for 2 minutes
  3. customthe mixture was separated by 7 ml of phosphate buffer (pH=6, 1 M)
  4. customThe organic layer was collected
  5. customthe aqueous layer was separated by 15 ml of a dichloromethane/ethanol solution (5:1) twice
  6. customthe organic layers were collected
  7. additionsodium sulfate was added
  8. customfor drying
  9. customSodium sulfate was then removed by filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=65:35→100:0)

Sources & evidence

ORD record
ord-4570f8b38cb7440da0b23e559fa94a11
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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