1-Pentyne → rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-(pentin-1-yl)-propionylamino}phthalide

HRID 2217747Notes

Reaction equation

HRID 2217747 reaction equation
[CH:1]#[C:2][CH2:3][CH2:4][CH3:5].[Li]CCCC.[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=1[C:22]1([CH2:25][C:26](=[O:40])[C:27]([NH:29][C:30]2[CH:31]=[C:32]3[C:37](=[CH:38][CH:39]=2)[C:35](=[O:36])[O:34][CH2:33]3)=[O:28])[CH2:24][CH2:23]1.[Cl-].[NH4+]>C1COCC1>[OH:40][C:26]([C:1]#[C:2][CH2:3][CH2:4][CH3:5])([CH2:25][C:22]1([C:13]2[CH:14]=[C:15]([C:18]([F:21])([F:19])[F:20])[CH:16]=[CH:17][C:12]=2[F:11])[CH2:24][CH2:23]1)[C:27]([NH:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[C:35](=[O:36])[O:34][CH2:33]2)=[O:28]

Participants

6

Reactant 4

HCID 123091-PentyneHCID 25517Ammonium ChlorideHCID 688712075-{3-[1-(2-Fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxo-propionylamino}-phthalideHCID 178418339Butyllithium

Product 1

HCID 58900311rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-(pentin-1-yl)-propionylamino}phthalide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution that consists of 1-pentyne (0.94 ml) in THF (9 ml) was mixed at −78° C. with nBuLi (0.6 ml, 1.6 M in hexane). It was allowed to stir for 30 minutes at −78° C., and then a solution of 5-{3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxopropionylamino}phthalide (200 mg) in 3 ml of tetrahydrofuran was added. Then, it was allowed to come to 23° C. over about 3 hours, and it was stirred for 10 more hours at this temperature. Then, the reaction mixture was poured into ice-cold, saturated ammonium chloride solution. It was extracted with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution and dried on sodium sulfate. The crude product was chromatographed on silica gel. 130 mg of product was obtained.

Workup

  1. waitto come to 23° C. over about 3 hours
  2. stirringit was stirred for 10 more hours at this temperature
  3. extractionIt was extracted with ethyl acetate
  4. washThe combined organic phases were washed with saturated sodium chloride solution
  5. customdried on sodium sulfate
  6. customThe crude product was chromatographed on silica gel

Sources & evidence

ORD record
ord-e2804a25e87146d99b97bf44ed998b56
Source dataset
uspto-grants-2008_08
Patent number
US07408060B2

Reaction notes

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