Hydrochloric Acid → HCID 89699859, compound

HRID 1055651Notes

Reaction equation

HRID 1055651 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([S:11]([F:16])([F:15])([F:14])([F:13])[F:12])[CH:10]=1)[C:5]([OH:7])=[O:6].Br[CH2:18][CH2:19][CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.O.[OH-].[Li+]>CN(C=O)C.C(OCC)(=O)C.O>[C:24]([O:23][C:22]([NH:21][CH2:20][CH2:19][CH2:18][O:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([S:11]([F:16])([F:12])([F:13])([F:14])[F:15])[CH:10]=1)[C:5]([OH:7])=[O:6])=[O:28])([CH3:27])([CH3:26])[CH3:25]

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 10796Cesium carbonateHCID 168937Lithium hydroxide, monohydrateHCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 581367943-Hydroxy-5-(pentafluorosulfanyl)benzoic acid

Product 1

HCID 89699859HCID 89699859, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under argon, 1.25 g (4.73 mmol) of the compound of Example 24A were combined with 1.46 g (6.2 mmol) of tert-butyl (3-bromopropyl)carbamate and 4.62 g (14.2 mmol) of caesium carbonate in 25 ml of DMF and stirred at RT until the reaction had gone to completion. The reaction was then acidified with 4 M hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was taken up in 25 ml of THF and 12 ml of water and, after addition of 596 mg (14.2 mmol) of lithium hydroxide monohydrate, stirred at 40° C. for 4 h. After the reaction had ended, water and ethyl acetate were added and the mixture was adjusted to pH 2 with 1 M hydrochloric acid. The organic phase was separated off, dried over magnesium sulphate, filtered and concentrated on a rotary evaporator. The crude product was purified by preparative HPLC (Method 19). This gave 1.64 g (92% pure, 76% of theory) of the title compound.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic phase was dried over magnesium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. stirringstirred at 40° C. for 4 h
  6. customThe organic phase was separated off
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated on a rotary evaporator
  10. customThe crude product was purified by preparative HPLC (Method 19)

Sources & evidence

ORD record
ord-51eb42ba8f074dd39a9d15e1ee10a3b6
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

Loading…