Hydrochloric Acid → HCID 69963137, compound

HRID 1280111Notes

Reaction equation

HRID 1280111 reaction equation
FC1C(F)=CC=C([N+]([O-])=O)C=1OC[C@H](O[Si](C)(C)C)C.[F:21][C:22]1[C:36]([F:37])=[CH:35][CH:34]=[C:33]([N+:38]([O-:40])=[O:39])[C:23]=1[O:24][C@@H:25]([CH3:32])[CH2:26][O:27][Si](C)(C)C.Cl>C(Cl)Cl.CO.CO>[F:21][C:22]1[C:36]([F:37])=[CH:35][CH:34]=[C:33]([N+:38]([O-:40])=[O:39])[C:23]=1[O:24][C@@H:25]([CH3:32])[CH2:26][OH:27]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 69965272HCID 69965272, compoundHCID 69965434HCID 69965434, compound

Product 1

HCID 69963137HCID 69963137, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

The mixture obtained from the above reaction, comprising (R)-1-(2,3-difluoro-6-nitrophenoxy)-2-trimethylsiloxypropane (1) and (S)-2-(2,3-difluoro-6-nitrophenoxy)-1-trimethylsiloxypropane (2), was dissolved in 200 mL of 10:1 CH2Cl2/MeOH at 0° C., and was treated with 5 mL of IM HCl in MeOH with stirring. The cooling bath was removed, and the mixture was aged for 30 minutes. The product mixture, which included (R)-1-(2,3-difluoro-6-nitrophenoxy)propan-2-ol formed by the desilylation of 1 and (S)-2-(2,3-difluoro-6-nitrophenoxy)-propane-1-ol formed by the desilylation of 2, was concentrated to a yellow oil, which was dried under high vacuum to remove the solvent. After concentration, the residue was dissolved in dichloromethane, and triphenylmethyl chloride (trityl chloride, 4 equivalents based on the undesired alcohol regioisomer (S)-2-(2,3-difluoro-6-nitrophenoxy)propane-1-ol) was added, followed by pyridine (1 equivalent based on the triphenylmethyl chloride). The mixture was stirred at ambient temperature, and the progress of the reaction was followed by gas chromatographic analysis. When the product regioisomer ratio, i.e., the ratio of (R)-1-(2,3-difluoro-6-nitrophenoxy)propan-2-ol to the triphenylmeythylated (S)-2-(2,3-difluoro-6-nitrophenoxy)propane-1-ol reached >100:<1, the reaction was concentrated to dryness. The oily residue was then purified by distillation as before, using a wiped film evaporator. The compound that distilled was (R)-1-(2,3-difluoro-6-nitrophenoxy)propan-2-ol, which is the desilylated alcohol derived from 1. The triphenylmeythylated (S)-2-(2,3-difluoro-6-nitrophenoxy)propane-1-ol, i.e., (S)-2-(2,3-difluoro-6-nitrophenoxy)-1-triphenylmethyloxypropane did not distill. The overall yield for the three steps to produce (R)-1-(2,3-difluoro-6-nitrophenoxy)propan-2-ol was 90-95% based upon 2,3-difluoro-6-nitrophenol.

Workup

  1. customThe mixture obtained from the above reaction
  2. customThe cooling bath was removed

Sources & evidence

ORD record
ord-aae9cf97bb0645c095fbc2b88ce2738a
Source dataset
uspto-grants-2002_09
Patent number
US06448449B2

Reaction notes

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