(S)-ethyl 1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate → (S)-1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid

HRID 1948478Notes

Reaction equation

HRID 1948478 reaction equation
[OH:1][C@@H:2]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[N:25]=[C:24]([C:26]3[O:30][N:29]=[C:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:27]=3[C:37]([F:40])([F:39])[F:38])[O:23][N:22]=2)=[CH:17][CH:16]=1)[CH2:3][N:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([C:10]([O:12]CC)=[O:11])[CH2:5]1>Cl.C(#N)C>[OH:1][C@@H:2]([C:15]1[CH:16]=[CH:17][C:18]([C:21]2[N:25]=[C:24]([C:26]3[O:30][N:29]=[C:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:27]=3[C:37]([F:40])([F:39])[F:38])[O:23][N:22]=2)=[CH:19][CH:20]=1)[CH2:3][N:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([C:10]([OH:12])=[O:11])[CH2:5]1

Participants

4

Reactant 1

HCID 58374192(S)-ethyl 1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate

Product 1

HCID 50925337(S)-1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acidYield 42.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6342AcetonitrileSolvent

Procedure

(S)-Ethyl 1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate (89 mg, 0.16 mmol) was heated at 50° C. in 6N HCl (5 mL) in acetonitrile (5 mL). The reaction mixture was stirred overnight and then filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 36 mg of (S)-1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl) piperidine-3-carboxylic acid as a TFA salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.23 (2H, d, J=8.35 Hz), 7.65-7.74 (4H, m), 7.54-7.65 (3H, m), 5.29 (1H, t, J=7.03 Hz), 4.00 (1H, br. s.), 3.43-3.75 (1H, m), 3.34-3.41 (2H, m), 2.82-3.24 (2H, m), 2.26 (1H, d, J=11.86 Hz), 1.84-2.14 (2H, m), 1.52-1.75 (1H, m). MS (m+1)=529. HPLC Peak RT=3.24 minutes. Purity=98%.

Workup

  1. filtrationfiltered
  2. custompurified by HPLC
  3. custom25 minute
  4. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-38377427c89a4aa0ac77150c608c1b37
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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