Triethylamine → Tert-butyl 1-(3-chloro-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

HRID 1804518Notes

Reaction equation

HRID 1804518 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]([OH:18])=O)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:35]=[CH:36][C:37]=1[C:38](=[N:40]O)[NH2:39])[CH2:23][N:24]1[CH2:27][CH:26]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:25]1.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C>CN(C)C=O.ClCCl>[Cl:19][C:20]1[CH:21]=[C:22]([CH:35]=[CH:36][C:37]=1[C:38]1[N:40]=[C:16]([C:10]2[O:9][N:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:11]=2[C:12]([F:13])([F:14])[F:15])[O:18][N:39]=1)[CH2:23][N:24]1[CH2:27][CH:26]([C:28]([O:30][C:31]([CH3:33])([CH3:34])[CH3:32])=[O:29])[CH2:25]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 583740941236188-80-9HCID 76816489tert-butyl 1-(3-chloro-4-(N'-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate

Product 1

HCID 67459175Tert-butyl 1-(3-chloro-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylateYield 22%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylic acid (1-D, 0.027 g, 0.105 mmol), tert-butyl 1-(3-chloro-4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (0.036 g, 0.105 mmol), BOP-Cl (0.035 g, 0.136 mmol), and triethylamine (0.044 mL, 0.315 mmol) in N,N-dimethylformamide (1 mL) was shaken on platform shaker at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was loaded on a fitted funnel containing a pad of CELITE® topped with a pad of silica gel, eluted with a 5% mixture of ethyl acetate in hexane, eluted with dichloromethane, and then eluted with a 20% mixture of ethyl acetate in hexane to give tert-butyl 1-(3-chloro-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (0.013 g, 0.023 mmol, 22% yield) as a white solid. The compound had an HPLC ret. time=2.13 min.−Column. CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=561.2.

Workup

  1. washwashed with a saturated aqueous solution of sodium bicarbonate
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was loaded on a fitted funnel
  5. additioncontaining a pad of CELITE®
  6. washeluted with a 5% mixture of ethyl acetate in hexane
  7. washeluted with dichloromethane
  8. washeluted with a 20% mixture of ethyl acetate in hexane

Sources & evidence

ORD record
ord-a6df3d38048446918a8e09da2694f989
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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