Diisopropylamine → HCID 67171008, compound

HRID 1506495Notes

Reaction equation

HRID 1506495 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH:13]([C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)/[C:20](=[N:24]/[OH:25])/[CH2:19][CH2:18]2)=[CH2:14].[C:26]1([C:32]2[O:36][N:35]=[C:34]([C:37](OC)=[O:38])[C:33]=2[C:41]([F:44])([F:43])[F:42])[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]3([OH:38])[O:25][N:24]=[C:20]4[C:21]5[C:17]([CH2:18][CH:19]34)=[CH:16][C:15]([CH:13]=[CH2:14])=[CH:23][CH:22]=5)[C:33]=2[C:41]([F:43])([F:44])[F:42])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 67168162HCID 67168162, compound2×HCID 87295219(NE)-N-(5-ethenyl-2,3-dihydroinden-1-ylidene)hydroxylamineHCID 178418339Butyllithium

Product 1

HCID 67171008HCID 67171008, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of diisopropylamine (0.441 mL, 3.10 mmol) in anhydrous THF (2 mL) was added n-BuLi (1.239 mL, 3.10 mmol) (2.5M solution in hexanes) dropwise at 0° C. under nitrogen. The pale yellow solution was then stirred at the same temperature for 20 min. before a solution of (E)-5-vinyl-2,3-dihydro-1H-inden-1-one oxime (Preparation 87B, 0.249 g, 1.438 mmol) in anhydrous THF (1 mL) was added dropwise at 0° C. under nitrogen. The mixture was stirred at 0° C. for 1 h and then a solution of methyl 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylate (Intermediate 1-5, 0.3 g, 1.106 mmol) in anhydrous THF (1 mL) was added dropwise at 0° C. The mixture was stirred at 0° C. for 70 min before being quenched with saturated aqueous ammonium chloride solution (3 mL) and water (3 mL). The mixture was extracted with EtOAc (2×30 mL). The EtOAc extracts were washed with brine (20 mL), dried over sodium sulfate and concentrated to yield a brown foamy solid. Flash chromatography purification (12 g silica gel column, 10→50% ethyl acetate in n-heptane) afforded 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-6-vinyl-3a,4-dihydro-3H-indeno[1,2-c]isoxazol-3-ol as a brown solid.

Workup

  1. additionwas added dropwise at 0° C. under nitrogen
  2. stirringThe mixture was stirred at 0° C. for 70 min
  3. custombefore being quenched with saturated aqueous ammonium chloride solution (3 mL) and water (3 mL)
  4. extractionThe mixture was extracted with EtOAc (2×30 mL)
  5. washThe EtOAc extracts were washed with brine (20 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customto yield a brown foamy solid
  9. customFlash chromatography purification (12 g silica gel column, 10→50% ethyl acetate in n-heptane)

Sources & evidence

ORD record
ord-a32b8becc78d4b17b21639936ca2c345
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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