Diisopropylethylamine → HCID 67457217, compound

HRID 1804451Notes

Reaction equation

HRID 1804451 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12](F)=[O:13])[C:8]=2[C:15]([F:18])([F:17])[F:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O/[N:20]=[C:21](/[C:23]1[CH:40]=[CH:39][C:26]([CH2:27][N:28]2[CH2:31][CH:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29]2)=[CH:25][CH:24]=1)\[NH2:22].CCN(C(C)C)C(C)C>C(#N)C>[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]3[O:13][N:22]=[C:21]([C:23]4[CH:24]=[CH:25][C:26]([CH2:27][N:28]5[CH2:29][CH:30]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:31]5)=[CH:39][CH:40]=4)[N:20]=3)[C:8]=2[C:15]([F:18])([F:17])[F:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 58374105HCID 58374105, compoundHCID 58504340HCID 58504340, compound

Product 1

HCID 67457217HCID 67457217, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 5-phenyl-4-(trifluoromethyl)isoxazole-3-carbonyl fluoride (100 mg, 0.386 mmol) and (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (Int.1, 118 mg, 0.386 mmol) in acetonitrile (2 mL) at room temperature was added Hunig's Base (0.081 mL, 0.463 mmol). The reaction mixture was stirred at room temperature for 3 days. The volatiles were removed under reduced pressure, and the residue was partitioned between dichloromethane (30 mL) and a saturated aqueous solution of sodium bicarbonate (30 mL). The aqueous layer was extracted with dichloromethane (2×20 mL), and the combined organic layers were dried over anhydrous magnesium sulfate and concentrated to afford a light yellow oil. The compound was purified by flash silica gel chromatography using a mixture of ethyl acetate/hexane (0-70%) to give tert-butyl 1-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (175 mg, 0.332 mmol, 86% yield) as a white, crystalline solid. The compound had an HPLC retention time=3.34 minutes (YMC-Combi 4.6×50 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS: (M+H)=527.13. 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (s, 9H), 3.26-3.33 (m, 3H), 3.54-3.59 (m, 2H), 3.70 (s, 2H), 7.46 (d, J=8.28 Hz, 2H), 7.56-7.62 (m, 2H), 7.63-7.68 (m, 1H), 7.78 (d, J=7.28 Hz, 2H), and 8.16 (d, 2H).

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customthe residue was partitioned between dichloromethane (30 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (2×20 mL)
  4. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. customto afford a light yellow oil
  7. customThe compound was purified by flash silica gel chromatography
  8. additiona mixture of ethyl acetate/hexane (0-70%)

Sources & evidence

ORD record
ord-ff2df1d319674af8b59bcf1b31ced87f
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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