Cyclopropylacetylene → HCID 54068872, compound

HRID 2298533Notes

Reaction equation

HRID 2298533 reaction equation
[CH:1]1([C:4]#[CH:5])[CH2:3][CH2:2]1.[Li]CCCC.[NH2:11][C:12]1[C:17]([F:18])=[CH:16][C:15]([Cl:19])=[CH:14][C:13]=1[C:20](=[O:25])[C:21]([F:24])([F:23])[F:22]>C1(C)C=CC=CC=1.C1COCC1>[NH2:11][C:12]1[C:17]([F:18])=[CH:16][C:15]([Cl:19])=[CH:14][C:13]=1[C:20]([OH:25])([C:5]#[C:4][CH:1]1[CH2:3][CH2:2]1)[C:21]([F:22])([F:23])[F:24]

Participants

6

Reactant 3

HCID 138823CyclopropylacetyleneHCID 18386558HCID 18386558, compoundHCID 178418339Butyllithium

Product 1

HCID 54068872HCID 54068872, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred, cooled (0° C.) solution of 2.0 mL (7.0 mmol) of 3.5 M cyclopropylacetylene in toluene was added 2 mL of THF followed by 2.8 mL (7.0 mmol) of 2.5 M n-BuLi in hexanes over 2 min. The solution was stirred 5 min. at 0° C., warmed to RT, and stirred a further 20 min. The reaction was cooled to 0° C. and treated with a solution of 300 mg (1.24 mmol) of 2′-amino-5′-chloro-3′-fluoro-2,2,2-trifluoroacetophenone in 3 mL of THF over 2 min. The solution was stirred an additional 10 min. and the cold bath was removed. The reaction was stirred 5 min and poured into 0.5 N citric acid. The mixture was extracted with ether, and the organic extract was washed with water then brine, dried (MgSO4), and concentrated under reduced pressure. Chromatography on silica gel (elution with hexanes then 3:1 hexanes-ether) afforded 185 mg (49%) of (+/−)-2-amino-5-chloro-3-fluoro-α-(cyclopropylethynyl)-α-(trifluoromethyl)benzyl alcohol as an off-white solid, mp 131-135° C. 1H NMR (300 MHz, CDCl3) δ7.34-7.36(m, 1H); 7.04(dd, 1H, J=10.4, 2.4 Hz); 4.58(br. s, 2H); 3.82(br. s, 1H); 1.35-1.44(m, 1H); 0.80-0.99(m, 4H). 19F NMR (282 MHz, CDCl3) δ−131.5(s, 1F), −80.5(s, 3F). High resolution mass spec: calculated for C13H11NOClF4(M+H)+: 308.0470, found: 308.0465.

Workup

  1. temperaturewarmed to RT
  2. stirringstirred a further 20 min
  3. temperatureThe reaction was cooled to 0° C.
  4. stirringThe solution was stirred an additional 10 min.
  5. customthe cold bath was removed
  6. stirringThe reaction was stirred 5 min
  7. additionpoured into 0.5 N citric acid
  8. extractionThe mixture was extracted with ether
  9. extractionthe organic extract
  10. washwas washed with water
  11. dry with materialbrine, dried (MgSO4)
  12. concentrationconcentrated under reduced pressure
  13. washChromatography on silica gel (elution with hexanes

Sources & evidence

ORD record
ord-8bb207bfe8fb420eaea1cbb7bc680196
Source dataset
uspto-grants-2002_12
Patent number
US06492515B2

Reaction notes

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