Diisopropylamine → HCID 67167591, compound

HRID 1506472Notes

Reaction equation

HRID 1506472 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH:13]([C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[C:21](=[O:25])[CH2:20][CH2:19][CH2:18]2)=[CH2:14].[C:26]1([C:32]2[O:36][N:35]=[C:34]([C:37](F)=[O:38])[C:33]=2[C:40]([F:43])([F:42])[F:41])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1>[C:26]1([C:32]2[O:36][N:35]=[C:34]([C:37]([CH:20]3[CH2:19][CH2:18][C:17]4[C:22](=[CH:23][CH:24]=[C:15]([CH:13]=[CH2:14])[CH:16]=4)[C:21]3=[O:25])=[O:38])[C:33]=2[C:40]([F:42])([F:43])[F:41])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 58374105HCID 58374105, compoundHCID 67167908HCID 67167908, compoundHCID 178418339Butyllithium

Product 1

HCID 67167591HCID 67167591, compoundYield 64.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a heat gun dried 100 mL 2-necked flask was added diisopropylamine (0.910 mL, 6.39 mmol) under a nitrogen atmosphere followed by THF (5 mL). The flask was cooled to 0° C. and n-BuLi (2.55 mL, 6.39 mmol) was added dropwise over a period of 2 min. The contents were stirred at 0° C. for 20 min., cooled to −78° C. and 6-vinyl-3,4-dihydronaphthalen-1(2H)-one (I-1B, 1 g, 5.81 mmol) dissolved in 2 mL of THF was added dropwise over a period of 3 min. The pale yellow reaction mixture was stirred at −78° C. for 20 min. Then 5-phenyl-4-(trifluoromethyl)isoxazole-3-carbonyl fluoride (I-14, 1.505 g, 5.81 mmol) dissolved in 2 mL of THF was added dropwise over a period of 2 min. The reaction mixture was stirred at −78° C. for 20 min, bought to room temperature and stirred at room temperature for 10 min. The reaction mixture was quenched with 1N HCl (5 mL) and extracted into EtOAc (20 mL). The aqueous layer was re-extracted with EtOAc (10 mL). The combined organic layers were dried over sodium sulfate concentrated and purified by column chromatography using an ISCO setup (80 g, RediSep® silica gel column). The desired fractions were collected and concentrated to yield 2-(5-phenyl-4-(trifluoromethyl)isoxazole-3-carbonyl)-6-vinyl-3,4-dihydronaphthalen-1(2H)-one (1.55 g, 3.77 mmol, 64.9% yield) as a yellow solid. LC/MS M+1=412.12.

Workup

  1. customTo a heat gun dried 100 mL 2-necked flask
  2. temperaturecooled to −78° C.
  3. additionwas added dropwise over a period of 3 min
  4. stirringThe pale yellow reaction mixture was stirred at −78° C. for 20 min
  5. additionwas added dropwise over a period of 2 min
  6. stirringThe reaction mixture was stirred at −78° C. for 20 min
  7. custombought to room temperature
  8. stirringstirred at room temperature for 10 min
  9. customThe reaction mixture was quenched with 1N HCl (5 mL)
  10. extractionextracted into EtOAc (20 mL)
  11. extractionThe aqueous layer was re-extracted with EtOAc (10 mL)
  12. dry with materialThe combined organic layers were dried over sodium sulfate
  13. concentrationconcentrated
  14. custompurified by column chromatography
  15. customThe desired fractions were collected
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-d78b9821094c4bd2a5a2ae8d5534af07
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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