p-Chlorophenethylic alcohol → HCID 58661638, compound

HRID 1392011Notes

Reaction equation

HRID 1392011 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH2:50])[C:5]2[N:6]=[CH:7][N:8]([C:48]=2[N:49]=1)[C@@H:9]1[O:47][C@H:34]([CH2:35][O:36][Si:37]([CH:44]([CH3:46])[CH3:45])([CH:41]([CH3:43])[CH3:42])[CH:38]([CH3:40])[CH3:39])[C@@H:22]([O:23][Si:24]([CH:31]([CH3:33])[CH3:32])([CH:28]([CH3:30])[CH3:29])[CH:25]([CH3:27])[CH3:26])[C@H:10]1[O:11][Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14].[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([CH2:58][CH2:59][OH:60])=[CH:54][CH:53]=1>>[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([CH2:58][CH2:59][O:60][C:2]2[N:3]=[C:4]([NH2:50])[C:5]3[N:6]=[CH:7][N:8]([C:48]=3[N:49]=2)[C@@H:9]2[O:47][C@H:34]([CH2:35][O:36][Si:37]([CH:38]([CH3:40])[CH3:39])([CH:41]([CH3:43])[CH3:42])[CH:44]([CH3:46])[CH3:45])[C@@H:22]([O:23][Si:24]([CH:31]([CH3:32])[CH3:33])([CH:28]([CH3:29])[CH3:30])[CH:25]([CH3:26])[CH3:27])[C@H:10]2[O:11][Si:12]([CH:19]([CH3:20])[CH3:21])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:14])[CH3:15])=[CH:54][CH:53]=1

Participants

3

Reactant 2

HCID 74647p-Chlorophenethylic alcoholHCID 58661648HCID 58661648, compound

Product 1

HCID 58661638HCID 58661638, compound

Conditions

Temperature
50 °C

Procedure

A mixture of 2-chloro-2′,3′,5′-tris-O-(triisopropylsilyl)adenosine (Example 6, 5.0 g) and 15 ml of 2-(4-chlorophenyl)ethyl alcohol was purged with nitrogen and heated to 50° C. Sodium hydride (1.56 g, 60% dispersion in mineral oil) was added at a rate so as to control gas evolution. After 48 hours of heating LC and LC/MS analysis showed a mixture of products with one and two protecting groups respectively (2 isomers). The reaction mixture was allowed to cool to room temperature and carefully quenched with 40 mL of water. The resulting mixture was extracted with ethyl acetate (70 ml). The layers were separated and the aqueous layer was again extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine (80 mL), dried over MgSO4 and concentrated under reduced pressure to afford a clear oil (18 g). This was purified by silica gel chromatography eluting progressively with CH2Cl2, 1%, 2%, 5% and then 10% MeOH in CH2Cl2. The fractions containing the desired products were combined and concentrated to yield 3.2 g of a gummy white solid. This mixture of silylated displacement products was taken to the next step.

Workup

  1. customwas purged with nitrogen
  2. additionSodium hydride (1.56 g, 60% dispersion in mineral oil) was added at a rate so as
  3. additiona mixture of products with one and two protecting groups respectively (2 isomers)
  4. temperatureto cool to room temperature
  5. customcarefully quenched with 40 mL of water
  6. extractionThe resulting mixture was extracted with ethyl acetate (70 ml)
  7. customThe layers were separated
  8. extractionthe aqueous layer was again extracted with ethyl acetate (2×50 mL)
  9. washThe combined organic phases were washed with brine (80 mL)
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b14d345d7e4948b4b9d8a162fa4e01d3
Source dataset
uspto-grants-2008_03
Patent number
US07342003B2

Reaction notes

Loading…