Diisopropylamine → HCID 22612323, compound

HRID 566443Notes

Reaction equation

HRID 566443 reaction equation
C(N[CH:5]([CH3:7])[CH3:6])(C)C.[CH2:8]([Li])[CH2:9][CH2:10]C.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.[O:20]1C[CH2:23][CH2:22][CH2:21]1>CCCCCC>[F:13][C:14]1[C:19]([C:21](=[O:20])[CH2:22][CH2:23][C:6]2[CH:5]=[CH:7][CH:10]=[CH:9][CH:8]=2)=[CH:18][CH:17]=[CH:16][N:15]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 8028Tetrahydrofuran2×HCID 97462-FluoropyridineHCID 178418339Butyllithium

Product 1

HCID 22612323HCID 22612323, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 2.33 mL (1.99 grams, 17.8 mmol) of diisopropylamine in 30 mL of tetrahydrofuran was cooled to −78° C. and treated dropwise with 7.12 mL (17.8 mmol) of a solution of 2.5 M n-butyllithium in hexane. When the addition was complete, the mixture was stirred for 5 minutes at −78° C. and treated dropwise with 1.53 mL (1.36 grams, 17.8 mmol) of freshly distilled 2-fluoropyridine. After the addition was complete, the yellow mixture was stirred for 15 minutes at −78° and treated dropwise with a solution of 3.44 grams (17.8 mmol) of the compound of Preparation 4 in 2 mL of THF. The mixture was stirred for 4 hours at −78° C. and then quenched by the addition of 5 mL of saturated aqueous ammonium chloride solution. After warming to room temperature, the mixture was partitioned between 175 mL of ethyl acetate and 150 mL of saturated aqueous ammonium chloride solution. The separated organic later was washed with brine (100 mL), dried (MgSO4), and evaporated to 3.49 grams of an orange oil. Purification by flash chromatography using a 25% EtOAc-hexane eluant afforded 940 mg (23%) of the title compound as a yellow oil. 1H NMR (CDCl3) d 3.05 (2H, t, J=7 Hz), 3.32-3.64 (2H, m), 7.17-7.33 (6H, m), 8.29-8.38 (2H, m); APCI MS (m/e) 229 (M+).

Workup

  1. additionWhen the addition
  2. additionAfter the addition
  3. stirringthe yellow mixture was stirred for 15 minutes at −78°
  4. stirringThe mixture was stirred for 4 hours at −78° C.
  5. customquenched by the addition of 5 mL of saturated aqueous ammonium chloride solution
  6. temperatureAfter warming to room temperature
  7. customthe mixture was partitioned between 175 mL of ethyl acetate and 150 mL of saturated aqueous ammonium chloride solution
  8. washThe separated organic later was washed with brine (100 mL)
  9. dry with materialdried (MgSO4)
  10. customevaporated to 3.49 grams of an orange oil
  11. customPurification by flash chromatography

Sources & evidence

ORD record
ord-87df379ffbee47daa1b0d80bc0b38a57
Source dataset
uspto-grants-2001_01
Patent number
US06174895B1

Reaction notes

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