Cyclopropylacetylene → (1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide

HRID 389414Notes

Reaction equation

HRID 389414 reaction equation
C([Li])CCC.[CH:6]1([C:9]#[CH:10])[CH2:8][CH2:7]1.[CH3:11][C@:12]12[C:18]([CH3:20])([CH3:19])[C@:15]([C:21]([N:23](C([C@@]34C(C)(C)[C@@](C)(CC3)C(=O)O4)=O)[C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=3[C:31](=[O:36])[C:32]([F:35])([F:34])[F:33])=[O:22])([CH2:16][CH2:17]1)[O:14][C:13]2=[O:50]>O1CCCC1>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([NH:23][C:21]([C@@:15]23[C:18]([CH3:19])([CH3:20])[C@@:12]([CH3:11])([CH2:17][CH2:16]2)[C:13](=[O:50])[O:14]3)=[O:22])=[C:25]([C@@:31]([OH:36])([C:10]#[C:9][CH:6]2[CH2:8][CH2:7]2)[C:32]([F:33])([F:34])[F:35])[CH:26]=1

Participants

5

Reactant 3

HCID 138823CyclopropylacetyleneHCID 66889383N,N-bis((1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl)-4-chloro-2-(2,2,2-trifluoroacetyl)anilineHCID 178418339Butyllithium

Product 1

HCID 50916497(1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2.5M n-Butyllithium (2.05 mL, 5.14 mmol) was added slowly to a solution of cyclopropyl acetylene (0.34 g, 5.14 mmol) in tetrahydrofuran (4 mL) in an ice-salt-bath under argon, and then N,N-bis((1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl)-4-chloro-2-(2,2,2-trifluoroacetyl)aniline (11, 1 g, 1.71 mmol) in THF (2 mL) was added. The reaction mixture was stirred for 1 hour. The reaction was quenched with 10% citric acid aqueous, the mixture was extracted with ethyl acetate and the two layers were separated. The organic layer was evaporated to dryness to give a crude oil and further crystallized with ethyl acetate and petroleum ether to give pure (1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide (10).

Workup

  1. customThe reaction was quenched with 10% citric acid aqueous
  2. extractionthe mixture was extracted with ethyl acetate
  3. customthe two layers were separated
  4. customThe organic layer was evaporated to dryness
  5. customto give a crude oil
  6. customfurther crystallized with ethyl acetate and petroleum ether

Sources & evidence

ORD record
ord-da5d64ba92754324977e32a9e7f82b2d
Source dataset
uspto-grants-2013_02
Patent number
US08378143B2

Reaction notes

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