Cyanomethylenetributylphosphorane → tert-butyl(9aS)-3-(3-cyano-2,4-difluorophenyl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

HRID 1502013Notes

Reaction equation

HRID 1502013 reaction equation
[C:1]([C:3]1[C:4]([F:28])=[C:5]([CH:10](O)[CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][C@H:13]2[CH2:25][OH:26])[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].C(C=P(CCCC)(CCCC)CCCC)#N>C1C=CC=CC=1>[C:1]([C:3]1[C:4]([F:28])=[C:5]([CH:10]2[O:26][CH2:25][C@@H:13]3[CH2:14][N:15]([C:18]([O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[O:19])[CH2:16][CH2:17][N:12]3[CH2:11]2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2]

Participants

4

Reactant 2

HCID 4622928CyanomethylenetributylphosphoraneHCID 86727062HCID 86727062, compound

Product 1

HCID 86727063tert-butyl(9aS)-3-(3-cyano-2,4-difluorophenyl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl (3S)-4-[2-(3-cyano-2,4-difluorophenyl)-2-hydroxyethyl]-3-(hydroxymethyl)piperazine-1-carboxylate (1.2 g, 3.0 mmol) and cyanomethylenetri-n-butylphosphorane (1.31 g, 5.44 mmol) were dissolved in 5 mL of benzene. The reaction mixture was degassed and heated to 100° C. for 16 h. LC-MS analysis showed product peak at 2.07 min (M+1=380). The reaction was cooled and evaporated to dryness. The residue was purified by MPLC chromatography through an 80 g Redi-sep column eluting with a 40% EtOAc/60% hexane mixture to yield a cis-trans mixture of the title compound.

Workup

  1. customThe reaction mixture was degassed
  2. customat 2.07 min
  3. temperatureThe reaction was cooled
  4. customevaporated to dryness
  5. customThe residue was purified by MPLC chromatography through an 80 g Redi-sep column
  6. washeluting with a 40% EtOAc/60% hexane mixture
  7. customto yield

Sources & evidence

ORD record
ord-7696e789dbb14713928cc7d2a5e9f623
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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