Sodium Iodide → tert-butyl (3S)-3-methyl-4-[6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]piperazine-1-carboxylate

HRID 1191914Notes

Reaction equation

HRID 1191914 reaction equation
Cl[CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=2)[CH2:4][CH2:3]1.[CH3:15][C@@H:16]1[NH:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1.[I-].[Na+].C(N(CC)CC)C>CN(C=O)C.O>[CH3:15][C@@H:16]1[N:21]([CH:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=3)[CH2:4][CH2:3]2)[CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH2:17]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 7023035(S)-1-Boc-3-methylpiperazineHCID 592126531-Chloro-6-(trifluoromethyl)indane

Product 1

HCID 59212635tert-butyl (3S)-3-methyl-4-[6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 1-chloro-6-(trifluoromethyl)indane (1.52 g, 6.89 mmol), tert-butyl (3S)-3-methylpiperazine-1-carboxylate (2.1 g, 10 mmol), sodium iodide (3 g, 20 mmol) and triethylamine (3 g, 30 mmol) in DMF (20 mL) was stirred at 60° C. overnight. After cooling to room temperature, water was added. The resulting solution was extracted with EtOAc twice. The combined extracts were washed with water and brine, dried over MgSO4 and concentrated. Column chromatography on silica (10%-30% EtOAc in hexane) afforded two isomers. Isomer 1: 0.52 g (brown oil). MS calculated for C20H27F3N2O2: (M+H)+ 385. found 385.2. Isomer 2: 0.41 g (brown oil). MS: (M+H)+ 385.2

Workup

  1. extractionThe resulting solution was extracted with EtOAc twice
  2. washThe combined extracts were washed with water and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customColumn chromatography on silica (10%-30% EtOAc in hexane) afforded two isomers

Sources & evidence

ORD record
ord-91c9c8eba6ef4407a195b2efa27aac61
Source dataset
uspto-grants-2014_03
Patent number
US08680104B2

Reaction notes

Loading…