1,2-Dichloroethane → HCID 58537216, compound

HRID 1804486Notes

Reaction equation

HRID 1804486 reaction equation
[C:1]1([C:7]2[C:11]([CH2:12][CH2:13][CH3:14])=[C:10]([C:15]([OH:17])=O)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li].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].C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C(Cl)CCl>CN(C=O)C>[C:1]1([C:7]2[C:11]([CH2:12][CH2:13][CH3:14])=[C:10]([C:15]3[O:17][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)[O:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 6

HCID 111,2-Dichloroethane2×HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 3028194LithiumHCID 58504340HCID 58504340, compoundHCID 58537210HCID 58537210, compound

Product 1

HCID 58537216HCID 58537216, compoundYield 43.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-phenyl-4-propylisoxazole-5-carboxylic acid, lithium salt (23.12 mg, 0.1 mmol), (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate, Int.1 (30.5 mg, 0.1 mmol), HOBT (16.85 mg, 0.110 mmol), diisopropylethylamine (0.044 mL, 0.250 mmol) and EDC (23.00 mg, 0.120 mmol) was stirred in DMF (1 mL) at rt for 18 hr. Additional EDC (23.00 mg, 0.120 mmol) was added and the reaction mixture was stirred at 60° C. for 5 hr. The reaction mixture was partitioned between EtOAc (30 mL) and saturated sodium bicarbonate solution (30 mL). The organic layer was washed with water (2×25 mL), brine (25 mL), dried (MgSO4) and concentrated to afford an 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 product were concentrated to afford tert-butyl 1-(4-(5-(3-phenyl-4-propylisoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (22 mg, 0.044 mmol, 43.9% yield) as a colorless oil. HPLC retention time=1.84 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)=501.21.

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 (2×25 mL), brine (25 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto afford an 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 product
  9. concentrationwere concentrated

Sources & evidence

ORD record
ord-1bb4733bc13946baaf58209e8085f10f
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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