Sodium Iodide → HCID 86638555, compound

HRID 1807739Notes

Reaction equation

HRID 1807739 reaction equation
[OH:1][CH2:2][C@@H:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.Br[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([OH:33])([C:29]([F:32])([F:31])[F:30])[C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=1.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.ClCCl>[F:26][C:25]([F:27])([F:28])[C:24]([C:21]1[CH:22]=[CH:23][C:18]([CH2:17][N:8]2[CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4][C@@H:3]2[CH2:2][OH:1])=[CH:19][CH:20]=1)([OH:33])[C:29]([F:30])([F:32])[F:31]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 235273962-[4-(Bromomethyl)phenyl]-1,1,1,3,3,3-hexafluoropropan-2-olHCID 24820286tert-Butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate

Product 1

HCID 86638555HCID 86638555, compoundYield 49.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (R)-tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (231 mg, 1.07 mmol), 2-(4-(bromomethyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (400 mg, 1.19 mmol) and sodium iodide (18 mg, 0.12 mmol) in acetonitrile (10 mL) was added potassium carbonate (655 mg, 4.75 mmol). The reaction mixture was stirred at room temperature for 3 days, before being diluted with dichloromethane (10 mL), filtered through cotton wool and concentrated under reduced pressure. The residue was purified by flash column chromatography (eluting with dichloromethane to 10% methanol in dichloromethane) to afford the intermediate (R)-tert-butyl 4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-3-(hydroxymethyl)piperazine-1-carboxylate (250 mg, 0.53 mmol). To a stirred solution of (R)-tert-butyl 4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-3-(hydroxymethyl)piperazine-1-carboxylate (220 mg, 0.466 mmol) in dichloromethane (3 mL), was added trifluoroacetic acid (3 mL, 38.3 mmol). The reaction mixture was stirred at room temperature for 5 hours before being purified directly by SCX chromatography, eluting with 2N ammonia in methanol solution to afford the title compound (165 mg). MS (ESI) m/z 373.3 [M+H]+

Workup

  1. filtrationfiltered through cotton wool
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by flash column chromatography (eluting with dichloromethane to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-bf3e6ee830ad4e87a03ff9ca3c53c181
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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