Trifluoroacetic acid → HCID 58071896, compound

HRID 870547Notes

Reaction equation

HRID 870547 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:7][N:6]([C@@H](C2C=CC=CC=2)C)[C:5](=[O:16])[CH2:4]1.[H-].[Na+].Cl[C:20]1[N:29]=[C:28]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[C:32]([O:38][CH3:39])[CH:31]=2)[CH:27]=[C:26]2[C:21]=1[CH:22]=[CH:23][CH:24]=[N:25]2.FC(F)(F)C(O)=O>CC(N(C)C)=O.O.C(#N)C>[CH3:39][O:38][C:32]1[CH:31]=[C:30]([C:28]2[CH:27]=[C:26]3[C:21]([CH:22]=[CH:23][CH:24]=[N:25]3)=[C:20]([O:1][CH2:2][C@H:3]3[CH2:7][NH:6][C:5](=[O:16])[CH2:4]3)[N:29]=2)[CH:35]=[CH:34][C:33]=1[O:36][CH3:37]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 13422564(4R)-4-(Hydroxymethyl)-1-[(1R)-1-phenylethyl]pyrrolidin-2-oneHCID 58071939HCID 58071939, compound

Product 1

HCID 58071896HCID 58071896, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 31374DimethylacetamideSolvent

Procedure

100 mg (R)-4-(hydroxymethyl)-1-((R)-1-phenylethyl)pyrrolidine-2-one (2.1) was placed in 2 mL dimethylacetamide and 20 mg sodium hydride (60%) were added and the mixture was stirred for 15 min at ambient temperature. Then 100 mg 6.37 was added and the mixture was stirred for 3 h at 50° C., further 4 h at 80° C. and overnight at 50° C. The reaction mixture was purified by chromatography (RP-HPLC-MS). The corresponding fractions were freeze-dried to provide protected Example 78 as intermediate. The intermediate was then treated with 2 mL of trifluoroacetic acid and heated for 30 min at 160° C. in the microwave. The reaction mixture was diluted with water and acetonitrile and purified by chromatography (RP-HPLC-MS). The corresponding fractions were freeze-fried.

Workup

  1. stirringthe mixture was stirred for 3 h at 50° C., further 4 h at 80° C. and overnight at 50° C
  2. customThe reaction mixture was purified by chromatography (RP-HPLC-MS)
  3. customThe corresponding fractions were freeze-dried
  4. customto provide
  5. temperatureheated for 30 min at 160° C. in the microwave
  6. custompurified by chromatography (RP-HPLC-MS)

Sources & evidence

ORD record
ord-20371961a842498e9cd7562ef1a1c289
Source dataset
uspto-grants-2015_03
Patent number
US08969568B2

Reaction notes

Loading…