Trimethyl orthoformate → 2-Bromo-1-[3-(pentafluorosulfanyl)-5-pyrrolidin-1-ylphenyl]ethanone

HRID 1258537Notes

Reaction equation

HRID 1258537 reaction equation
[F:1][S:2]([F:20])([F:19])([F:18])([F:17])[C:3]1[CH:4]=[C:5]([C:14](=[O:16])[CH3:15])[CH:6]=[C:7]([N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:8]=1.C(OC)(OC)OC.CC1(C)[C@]2(CS(O)(=O)=O)C(C[C@H]1CC2)=O.[Br-:43].[Br-].[Br-].C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1>CO.C1COCC1>[Br:43][CH2:15][C:14]([C:5]1[CH:6]=[C:7]([N:9]2[CH2:10][CH2:11][CH2:12][CH2:13]2)[CH:8]=[C:3]([S:2]([F:1])([F:17])([F:18])([F:19])[F:20])[CH:4]=1)=[O:16]

Participants

7

Reactant 4

HCID 9005Trimethyl orthoformateHCID 65617D-Camphorsulfonic AcidHCID 17977687Phenyltrimethylammonium bromide dibromideHCID 581374371-[3-(Pentafluorosulfanyl)-5-pyrrolidin-1-ylphenyl]ethanone

Product 1

HCID 581374592-Bromo-1-[3-(pentafluorosulfanyl)-5-pyrrolidin-1-ylphenyl]ethanoneYield 17.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-[3-(Pentafluorosulfanyl)-5-pyrrolidin-1-ylphenyl]ethanone (78 mg) was dissolved in methanol (5 ml) and admixed while stirring with trimethyl orthoformate (80 mg) and DL-10-camphorsulfonic acid (57 mg). After stirring at RT for 3 h, THF (5 ml) was added, followed by phenyltrimethylammonium tribromide (83 mg). After stirring at RT for 3 h, the mixture was left to stand overnight. Then the mixture was heated to 50° C. for 3 h and subsequently dried. The residue was taken up in ACN, admixed with 2N sulfuric acid and stirred for 30 min. Then it was admixed with water and concentrated. The residue was purified by means of preparative HPLC. The product-containing fractions were combined, freed of the acetonitrile, admixed with saturated sodium hydrogencarbonate solution and extracted three times with ethyl acetate. The combined extracts were dried over magnesium sulfate, filtered and concentrated. 9 mg of the desired compound were obtained.

Workup

  1. stirringAfter stirring at RT for 3 h
  2. waitthe mixture was left
  3. waitto stand overnight
  4. temperatureThen the mixture was heated to 50° C. for 3 h
  5. customsubsequently dried
  6. stirringstirred for 30 min
  7. concentrationconcentrated
  8. customThe residue was purified by means of preparative HPLC
  9. extractionextracted three times with ethyl acetate
  10. dry with materialThe combined extracts were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-4ee706fd6cfd42d58188d4ef8a0b80c0
Source dataset
uspto-grants-2013_06
Patent number
US08466169B2

Reaction notes

Loading…