1,2-Dichloroethane → HCID 58537219, compound

HRID 1804489Notes

Reaction equation

HRID 1804489 reaction equation
[F:1][CH:2]([F:17])[C:3]1[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:5][O:6][C:7]=1[C:8]([OH:10])=O.O/[N:19]=[C:20](/[C:22]1[CH:39]=[CH:38][C:25]([CH2:26][N:27]2[CH2:30][CH:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:28]2)=[CH:24][CH:23]=1)\[NH2:21].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(C(C)C)CC)(C)C>CN(C=O)C>[F:17][CH:2]([F:1])[C:3]1[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:5][O:6][C:7]=1[C:8]1[O:10][N:21]=[C:20]([C:22]2[CH:23]=[CH:24][C:25]([CH2:26][N:27]3[CH2:28][CH:29]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH2:30]3)=[CH:38][CH:39]=2)[N:19]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58504340HCID 58504340, compoundHCID 58537212HCID 58537212, compound

Product 1

HCID 58537219HCID 58537219, compoundYield 38.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of 4-(difluoromethyl)-3-phenylisoxazole-5-carboxylic acid (28 mg, 0.117 mmol), (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate, Int.1, (35.7 mg, 0.117 mmol), HOBT (28.7 mg, 0.187 mmol), EDC (52.7 mg, 0.275 mmol) and diisopropylethylamine (82 μL, 0.468 mmol) in DMF was stirred at rt for 3 hr and at 55° C. for 18 hr. The reaction mixture was partitioned between EtOAc (30 ml) and saturated sodium bicarbonate solution (30 ml). The organic layer was washed with water (2×30 ml) and brine (30 ml). After drying (MgSO4) and filtration, the organic layer was concentrated to a yellow oil that was chromatographed on a 4 gm Isco silica gel cartridge, eluting with a 0-50% EtOAc/Hex gradient. The essentially pure fractions containing the product were concentrated to afford tert-butyl 1-(4-(5-(4-(difluoromethyl)-3-phenylisoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (23 mg, 0.045 mmol, 38.6% yield) as a white solid. HPLC retention time=1.80 minutes (PHENOMENEX® Luna 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1% TFA over a 2 minute gradient. MS: (M+H)=509.14.

Workup

  1. customThe reaction mixture was partitioned between EtOAc (30 ml) and saturated sodium bicarbonate solution (30 ml)
  2. washThe organic layer was washed with water (2×30 ml) and brine (30 ml)
  3. customAfter drying
  4. filtration(MgSO4) and filtration
  5. concentrationthe organic layer was concentrated to a yellow oil that
  6. customwas chromatographed on a 4 gm Isco silica gel cartridge
  7. washeluting with a 0-50% EtOAc/Hex gradient
  8. additionThe essentially pure fractions containing the product
  9. concentrationwere concentrated

Sources & evidence

ORD record
ord-54cb63bd821e474590b17ba52e9046ce
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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