Hydrochloric Acid → 2-((3R)-1-(2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetic acid

HRID 1948526Notes

Reaction equation

HRID 1948526 reaction equation
[OH:1][CH:2]([C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:26]=[C:25]([C:27]3[C:31]([C:32]([F:35])([F:34])[F:33])=[C:30]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[O:29][N:28]=3)[O:24][N:23]=2)=[CH:18][CH:17]=1)[CH2:3][N:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([CH2:10][C:11]([O:13]CC)=[O:12])[CH2:5]1.Cl>C(#N)C>[OH:1][CH:2]([C:16]1[CH:17]=[CH:18][C:19]([C:22]2[N:26]=[C:25]([C:27]3[C:31]([C:32]([F:35])([F:34])[F:33])=[C:30]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[O:29][N:28]=3)[O:24][N:23]=2)=[CH:20][CH:21]=1)[CH2:3][N:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([CH2:10][C:11]([OH:13])=[O:12])[CH2:5]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66955235HCID 66955235, compound

Product 1

HCID 509237082-((3R)-1-(2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetic acidYield 96.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of ethyl 2-((3R)-1-(2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetate (72 mg, 0.126 mmol) in acetonitrile (5 mL) was added 6N HCl (5 mL). The reaction mixture was stirred at room temperature for 3 days. 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 66 mg of 2-((3R)-1-(2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetic acid as a TFA salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.12 (2H, d, J=8.35 Hz), 7.71 (2H, d, J=7.47 Hz), 7.49-7.66 (5H, m), 5.16 (1H, dd, J=9.67, 4.39 Hz), 3.81 (1H, d, J=11.86 Hz), 3.56 (1H, d, J=11.42 Hz), 3.14-3.33 (2H, m), 2.83-2.94 (1H, m), 2.72 (1H, t, J=11.86 Hz), 2.16-2.38(3H, m), 1.78-1.92 (3H, m), 1.10-1.33 (1H, m). MS (m+1)=543. HPLC Peak RT=3.24 minutes (Analytical Method A). Purity=98%.

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompurified by HPLC
  3. custom25 minute
  4. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-857d7c5e2beb4e5c8c5b6a8bc5192166
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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