Trifluoroacetic acid → HCID 178487209, compound

HRID 2202308Notes

Reaction equation

HRID 2202308 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:10]=[C:11]([NH:19][C:20]([C@H:22]2[C:31]3[C:26](=[CH:27][C:28]([O:32][CH3:33])=[CH:29][CH:30]=3)[CH2:25][CH2:24][N:23]2[C:34]([C@@H:36]2[CH2:39][C@H:38]([CH2:40][C:41]([O:43]C(C)(C)C)=[O:42])[CH2:37]2)=[O:35])=[O:21])[CH:12]=[CH:13][C:14]=1[Si:15]([CH3:18])([CH3:17])[CH3:16].C(=O)([O-])O.[Na+]>O.C(#N)C>[F:8][C:9]1[CH:10]=[C:11]([NH:19][C:20]([C@H:22]2[C:31]3[C:26](=[CH:27][C:28]([O:32][CH3:33])=[CH:29][CH:30]=3)[CH2:25][CH2:24][N:23]2[C:34]([C@@H:36]2[CH2:39][C@H:38]([CH2:40][C:41]([OH:43])=[O:42])[CH2:37]2)=[O:35])=[O:21])[CH:12]=[CH:13][C:14]=1[Si:15]([CH3:16])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 178487213HCID 178487213, compound

Product 1

HCID 178487209HCID 178487209, compoundYield 32.5%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

Cooled TFA (2.0 mL) was added to tert-butyl 2-(cis-3-((R)-1-((3-fluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutyl)acetate (160 mg, 0.28 mmol) at 0° C., and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was neutralized with ice and aqueous sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 20→90% ethyl acetate/hexane), and then preparative HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)) to give the title compound (46.9 mg, 0.091 mmol, 32.5%) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 20→90% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-db93bb0325f44e9fad4ae9e8e27516ef
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

Loading…