Diisopropylethylamine → HCID 53782845, compound

HRID 612798Notes

Reaction equation

HRID 612798 reaction equation
[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH3:14])[O:7][C@H:6]1[N:15]1[CH:22]=[C:21]([C:23]#[C:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:19]([NH2:20])=[N:18][C:16]1=[O:17])(=[O:3])[CH3:2].ClC(Cl)(O[C:33](=[O:39])[O:34][C:35](Cl)(Cl)Cl)Cl.[CH3:41][O:42][CH2:43][C:44](C)([CH3:47])[CH2:45]O.C(N(C(C)C)CC)(C)C>ClCCl.O.CO>[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH3:14])[O:7][C@H:6]1[N:15]1[CH:22]=[C:21]([C:23]#[C:24][Si:25]([CH3:26])([CH3:28])[CH3:27])[C:19]([NH:20][C:33]([O:34][CH2:35][C:44]([CH3:47])([CH3:45])[CH2:43][O:42][CH3:41])=[O:39])=[N:18][C:16]1=[O:17])(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 1434401-Propanol, 3-methoxy-2,2-dimethyl-HCID 18396487HCID 18396487, compound

Product 1

HCID 53782845HCID 53782845, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2',3'-di-O-acetyl-5'-deoxy-5-[2-(trimethylsilyl)-ethynyl]cytidine (100 mg, 0.25 mmol) and triphosgene (73 mg, 0.25 mmol) in dry dichloromethane (3 ml) there was added a solution of 3-methoxy-2,2-dimethylpropanol (77 mg, 0.65 mmol) [ref. Tetrahedron Asymmetry,1995,6, 271-282] and diisopropylethylamine (182 ml,1.3 mmol) in dry dichloromethane (2 ml). After stirring for 30 min at room temperature under Ar, methanol (0.5 ml) and water (0.5 ml) were added dropwise to the reaction mixture at room temperature. After stirring for an additional 5 minutes, the reaction mixture was partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous MgSO4 and filtered. The filtrate was evaporated under reduced pressure. Purification of the residue by preparative thin layer chromatography on silica gel (using n-hexane:ethyl acetate=1:1 as a developing solvent) gave 2',3'-di-O-acetyl-5'-deoxy- N4 -[(3-methoxy-2,2-dimethylpropoxy)carbonyl]-5-[2-(trimethylsilyl)ethynyl]-cytidine (107 mg,79%).

Workup

  1. additionwere added dropwise to the reaction mixture at room temperature
  2. customthe reaction mixture was partitioned between dichloromethane and water
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customThe filtrate was evaporated under reduced pressure
  8. customPurification of the residue by preparative thin layer chromatography on silica gel (

Sources & evidence

ORD record
ord-0533a8a93e7146ce80fc000999e37ef0
Source dataset
uspto-grants-1999_12
Patent number
US06005098

Reaction notes

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