Sodium Thiosulfate → Briciclib

HRID 2079491Notes

Reaction equation

HRID 2079491 reaction equation
[P:1]([O:38]CC1C=CC=CC=1)([O:30]CC1C=CC=CC=1)([O:3][C:4]1[CH:9]=[C:8]([CH2:10][S:11]([CH:14]=[CH:15][C:16]2[C:21]([O:22][CH3:23])=[CH:20][C:19]([O:24][CH3:25])=[CH:18][C:17]=2[O:26][CH3:27])(=[O:13])=[O:12])[CH:7]=[CH:6][C:5]=1[O:28][CH3:29])=[O:2].Br[Si](C)(C)C.[Na].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl>[P:1]([OH:38])([OH:30])([O:3][C:4]1[CH:9]=[C:8]([CH2:10][S:11](/[CH:14]=[CH:15]/[C:16]2[C:17]([O:26][CH3:27])=[CH:18][C:19]([O:24][CH3:25])=[CH:20][C:21]=2[O:22][CH3:23])(=[O:13])=[O:12])[CH:7]=[CH:6][C:5]=1[O:28][CH3:29])=[O:2]

Participants

6

Reactant 4

HCID 24477Sodium ThiosulfateHCID 76113BromotrimethylsilaneHCID 5360545SodiumHCID 729599055-((2,4,6-Trimethoxystyrylsulfonyl)methyl)-2-methoxy-phenyl dibenzyl phosphate

Product 1

HCID 11248490BriciclibYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxy-phenyl dibenzyl phosphate (4.36 g, 6.7 mmol) in anhydrous DCM (40 mL) under nitrogen at 0° C. was added bromotrimethylsilane (2.14 g, 2.1 eq). The resulting mixture was stirred for 45 minutes and monitored by TLC. sodium When the reaction was complete, aqueous sodium thiosulfate (1%, 50 mL) was added and the resulting mixture was stirred for an additional 5 minutes. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (3×25 mL). The combined organic extract was concentrated in vacuo to afford the crude 5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenyl dihydrogen phosphate. The product was purified column chromatography on silica eluted with a methanol/chloroform gradient to yield 1.4 g of the purified product having a melting point of 202-205° C.

Workup

  1. stirringthe resulting mixture was stirred for an additional 5 minutes
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (3×25 mL)
  4. extractionThe combined organic extract
  5. concentrationwas concentrated in vacuo
  6. customto afford the crude 5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenyl dihydrogen phosphate
  7. customThe product was purified column chromatography on silica
  8. washeluted with a methanol/chloroform gradient

Sources & evidence

ORD record
ord-1e0611e987e04a96909a37a01d6789c5
Source dataset
uspto-grants-2011_04
Patent number
US07932242B2

Reaction notes

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