Tetrahydrofuran → Tert-butyl 1-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

HRID 1941897Notes

Reaction equation

HRID 1941897 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:16]([O:18]/[N:19]=[C:20](/[C:22]3[CH:39]=[CH:38][C:25]([CH2:26][N:27]4[CH2:30][CH:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:28]4)=[CH:24][CH:23]=3)\[NH2:21])=O)[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].O1CCCC1>C(#N)C>[C:1]1([C:7]2[CH:8]=[C:9]([C:16]3[O:18][N:19]=[C:20]([C:22]4[CH:39]=[CH:38][C:25]([CH2:26][N:27]5[CH2:28][CH:29]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH2:30]5)=[CH:24][CH:23]=4)[N:21]=3)[S:10][C:11]=2[C:12]([F:13])([F:15])[F:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 141619525tert-butyl 1-[[4-[(Z)-N'-[4-phenyl-5-(trifluoromethyl)thiophene-2-carbonyl]oxycarbamimidoyl]phenyl]methyl]azetidine-3-carboxylate

Product 1

HCID 66678166Tert-butyl 1-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylateYield 72.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (Z)-tert-butyl 1-(4-(N′-(4-phenyl-5-(trifluoromethyl)thiophene-2-carbonyloxy)carbamimidoyl)benzyl)azetidine-3-carboxylate (744 mg, 1.33 mmol) in acetonitrile (30 mL) was added a 1M solution of TBAF in tetrahydrofuran (3.99 mL, 3.99 mmol), and the reaction mixture was allowed to stir at room temperature for 3 days. The volatiles were removed under reduced pressure, and the residue was chromatographed on a 5×12 cm silica gel column, eluting with a 0-50% EtOAc/Hex gradient. The essentially pure fractions containing product were concentrated to afford tert-butyl 1-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (521 mg, 0.962 mmol, 72.4% yield) as a colorless solid. HPLC ret. time=3.63 min. (YMC Combi S-5 4.6×50 mm ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS: (M+H)=542.22. 1H NMR (500 MHz, CDCl3) δ ppm 1.46 (s, 9H), 3.25-3.31 (m, 3H), 3.52-3.58 (m, 2H), 3.69 (s, 2H), 7.43 (d, J=8.25 Hz, 2H), 7.47 (m, 5H), 7.91 (s, d, J=1.65 Hz, 1H), and 8.09 (d, J=8.25 Hz, 2 H).

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customthe residue was chromatographed on a 5×12 cm silica gel column
  3. washeluting with a 0-50% EtOAc/Hex gradient
  4. additionThe essentially pure fractions containing product
  5. concentrationwere concentrated

Sources & evidence

ORD record
ord-4c01dde4b43c44718eb5800d4b1d81dc
Source dataset
uspto-grants-2013_03
Patent number
US08389509B2

Reaction notes

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