Tetrabutylammonium Fluoride → (4S,6S)-4-(5-ethynyl-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

HRID 930337Notes

Reaction equation

HRID 930337 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][Si](CC)(CC)CC)=[CH:4][C:3]=1[C@:17]1([CH2:28][F:29])[CH2:22][C@@H:21]([C:23]([F:26])([F:25])[F:24])[O:20][C:19]([NH2:27])=[N:18]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C@:17]2([CH2:28][F:29])[CH2:22][C@@H:21]([C:23]([F:24])([F:25])[F:26])[O:20][C:19]([NH2:27])=[N:18]2)[CH:4]=1)#[CH:9]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86732162(4S,6S)-4-(2-fluoro-5-((triethylsilyl)ethynyl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

Product 1

HCID 86732163(4S,6S)-4-(5-ethynyl-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amineYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (4S,6S)-4-(2-fluoro-5-((triethylsilyl)ethynyl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (1.285 g, 2.97 mmol from above) in 20 mL of THF was treated with tetrabutylammonium fluoride (1.0 M in THF) (3.27 mL, 3.27 mmol) at rt for 45 min. The solvent was removed under vacuum and the residue was dissolved in 2 mL of DCM and purified using the Shoko instrument with 40 g pre-packed silica gel column and EtOAc in hexanes as eluent (0-50% 20 min, 50% 10 min). Desired fractions were combined and concentrated to dryness to give the titled compound as a slightly colored oil: 0.905 g, 96% yield. MS m/z=319.0 [M+H]+. Calculated for C14H11F5N2O: 318.1.

Workup

  1. customThe solvent was removed under vacuum
  2. dissolutionthe residue was dissolved in 2 mL of DCM
  3. custompurified
  4. custom(0-50% 20 min, 50% 10 min)
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-f074ee6719ce4565940b206b7158595a
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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