Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl ester → (R,E)-ethyl 4-((2-chloro-5-fluoropyrimidin-4-yl)amino)-5,5-dimethylhex-2-enoate

HRID 2171845Notes

Reaction equation

HRID 2171845 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:10]=O)[C:5]([F:16])=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)=[CH:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])C=CC=CC=1>ClCCl>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([C:12]([CH3:15])([CH3:14])[CH3:13])/[CH:10]=[CH:24]/[C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:5]([F:16])=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 70670Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl esterHCID 86714733(S)-2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutanal2×

Product 1

HCID 86714739(R,E)-ethyl 4-((2-chloro-5-fluoropyrimidin-4-yl)amino)-5,5-dimethylhex-2-enoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutanal, 15a, (0.45 g, 1.84 mmol) in dichloromethane (9.0 mL) was added ethyl 2-triphenylphosphoranylideneacetate (0.96 g, 2.75 mmol). After allowing the reaction mixture to stir at room temperature overnight, approximately half of the solvent was removed under reduced pressure. The remaining crude mixture was purified by directly loading onto a silica gel column (0-100% EtOAc/hexanes) to afford 535 mg of the desired product: LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=3.41 minutes (M+H) 316.32.

Workup

  1. customapproximately half of the solvent was removed under reduced pressure
  2. customThe remaining crude mixture was purified

Sources & evidence

ORD record
ord-fb973e9a472b45b89163c6519e6eea97
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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