(Diethylamino)sulfur trifluoride → (3R,6R)-1-[(1R)-1-(2,4-Difluorophenyl)-2-(3-fluoroazetidin-1-yl)-2-oxoethyl]-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutylpiperazine-2,5-dione

HRID 2108713Notes

Reaction equation

HRID 2108713 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([N:17]1[C@H:22]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:21](=[O:27])[NH:20][C@H:19]([CH:28]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29]2)[C:18]1=[O:37])[C:10]([N:12]1[CH2:15][CH:14](O)[CH2:13]1)=[O:11].C(N(S(F)(F)[F:44])CC)C.C(=O)([O-])O.[Na+]>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([N:17]1[C@H:22]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:21](=[O:27])[NH:20][C@H:19]([CH:28]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29]2)[C:18]1=[O:37])[C:10]([N:12]1[CH2:13][CH:14]([F:44])[CH2:15]1)=[O:11]

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 11295207HCID 11295207, compound

Product 1

HCID 11226041(3R,6R)-1-[(1R)-1-(2,4-Difluorophenyl)-2-(3-fluoroazetidin-1-yl)-2-oxoethyl]-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutylpiperazine-2,5-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The azetidinol (Example 15) (57 mg) in anhydrous dichloromethane (2 mL) was stirred at −5° C. and diethylaminosulfur trifluoride (50 μL, excess) was added in one portion. The mixture was left at room temperature overnight and saturated aqueous sodium hydrogen carbonate (3 mL) was added. The mixture was diluted with dichloromethane (10 mL) and the organic phase was separated using a hydrophobic frit and blown down with nitrogen. The crude reaction mixture was purified using the mass-directed autoprep system to give (3R,6R)-1-[(1R)-1-(2,4-difluorophenyl)-2-(3-fluoroazetidin-1-yl)-2-oxoethyl]-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutylpiiierazine-2,5-dione (26 mg) as a white solid.

Workup

  1. customthe organic phase was separated
  2. customThe crude reaction mixture
  3. customwas purified
  4. customto give (3R,6R)-1-[(1R)-1-(2,4-difluorophenyl)-2-(3-fluoroazetidin-1-yl)-2-oxoethyl]-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutylpiiierazine-2,5-dione (26 mg) as a white solid

Sources & evidence

ORD record
ord-db68083f807448e8802530f1ad999b8f
Source dataset
uspto-grants-2009_04
Patent number
US07514437B2

Reaction notes

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