ethyl 2-(morpholin-3-yl)acetate → HCID 50923567, compound

HRID 1948518Notes

Reaction equation

HRID 1948518 reaction equation
[O:1]1[CH2:3][CH:2]1[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[C:13]([C:15]3[O:19][N:18]=[C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:16]=3[C:26]([F:29])([F:28])[F:27])[O:12][N:11]=2)=[CH:6][CH:5]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH:31]1[CH2:36][C:37]([O:39]CC)=[O:38]>C(O)C>[OH:1][CH:2]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:14]=[C:13]([C:15]3[O:19][N:18]=[C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:16]=3[C:26]([F:28])([F:27])[F:29])[O:12][N:11]=2)=[CH:8][CH:9]=1)[CH2:3][N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH:31]1[CH2:36][C:37]([OH:39])=[O:38]

Participants

4

Reactant 2

HCID 11789040ethyl 2-(morpholin-3-yl)acetateHCID 866563983-(4-(Oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole

Product 1

HCID 50923567HCID 50923567, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole, Preparation 28C (30 mg, 0.075 mmol) in ethanol (2 mL) was added ethyl 2-(morpholin-3-yl)acetate (52.1 mg, 0.301 mmol). The resulting mixture was heated at 80° C. overnight. Solvent was removed in vacuo. The residue was treated with 6N HCl/MeCN at 50° C. overnight. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 18 mg of 2-(4-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)morpholin-3-yl)acetic acid as a TFA salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.23 (2H, d, J=7.91 Hz), 7.72 (2H, dd, J=8.35, 2.20 Hz), 7.68 (2H, d, J=7.03 Hz), 7.53-7.65 (3H, m), 5.22-5.30 (1H, m), 3.61-4.21 (7H, m), 3.35-3.55 (2H, m), 2.88-3.10 (2H, m). MS (m+1)=545. HPLC Peak RT=3.23 minutes (Analytical Method A). Purity=93%.

Workup

  1. customSolvent was removed in vacuo
  2. additionThe residue was treated with 6N HCl/MeCN at 50° C. overnight
  3. filtrationThe reaction mixture was filtered
  4. custompurified by HPLC
  5. custom25 minute
  6. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-27efb774c6ef40e7a0e8e565e5b7837a
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

Loading…