Diisopropylethylamine → HCID 50923427, compound

HRID 1948507Notes

Reaction equation

HRID 1948507 reaction equation
[OH:1][CH:2]([C:15]1[CH:20]=[CH:19][C:18]([C:21](=[N:23][OH:24])[NH2:22])=[CH:17][CH:16]=1)[CH2:3][N:4]1[CH2:7][CH:6]([C:8]([O:10]C(C)(C)C)=[O:9])[CH2:5]1.CCN(C(C)C)C(C)C.[C:34]1([C:40]2[C:44]([C:45]([F:48])([F:47])[F:46])=[C:43]([C:49](F)=O)[O:42][N:41]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C(#N)C.C(OCC)(=O)C>[OH:1][CH:2]([C:15]1[CH:16]=[CH:17][C:18]([C:21]2[N:22]=[C:49]([C:43]3[O:42][N:41]=[C:40]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[C:44]=3[C:45]([F:48])([F:46])[F:47])[O:24][N:23]=2)=[CH:19][CH:20]=1)[CH2:3][N:4]1[CH2:5][CH:6]([C:8]([OH:10])=[O:9])[CH2:7]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 58374067HCID 58374067, compoundHCID 76738020tert-butyl 1-(2-hydroxy-2-(4-(N'-hydroxycarbamimidoyl)phenyl)ethyl)azetidine-3-carboxylate

Product 1

HCID 50923427HCID 50923427, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of tert-butyl 1-(2-hydroxy-2-(4-(N′-hydroxycarbamimidoyl)phenyl)ethyl)azetidine-3-carboxylate (111 mg, 0.33 mmol) and DIEA (0.115 mL, 0.660 mmol) in acetonitrile (10 mL) was added 3-phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl fluoride, Int-I-G (86 mg, 0.33 mmol). After 1 hour, TBAF (0.330 mL, 0.330 mmol) was added and the reaction was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with H2O. The organic layer was dried with MgSO4, filtered, and concentrated. Crude residue was treated with TFA/DCM to remove t-butyl ester. The resulting material was concentrated in vacuo and purified by HPLC to yield 36 mg of 1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)azetidine-3-carboxylic acid as the tetrabutylammonium salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.22 (2H, d, J=8.35 Hz), 7.68 (4H, d, J=8.35 Hz), 7.53-7.65 (3H, m), 5.04 (1H, dd, J=10.11, 3.08 Hz), 4.45 (4H, t, J=9.89 Hz), 3.73 (1H, br. s.), 3.36-3.62 (2H, m). MS (m+1)=501. HPLC Peak RT=3.23 minutes (Analytical Method A). Purity=98%.

Workup

  1. washwashed with H2O
  2. dry with materialThe organic layer was dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionCrude residue was treated with TFA/DCM
  6. customto remove t-butyl ester
  7. concentrationThe resulting material was concentrated in vacuo
  8. custompurified by HPLC

Sources & evidence

ORD record
ord-fb1e3ab7260148d7bb7458511111556e
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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