Piperidin-4-ol → HCID 71494897, compound

HRID 1487024Notes

Reaction equation

HRID 1487024 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([OH:22])=O)[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>C(Cl)Cl.O>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([N:25]3[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]3)=[O:22])[N:14]=2)[CH:4]=[C:3]([C:2]([F:24])([F:23])[F:1])[CH:8]=1

Participants

7

Reactant 4

HCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 71494897HCID 71494897, compoundYield 10.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-60 °C

Procedure

(Z)-3-(3-(3,5-Bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.20 g, 1.0 eq.) was dissolved in DCM (10 mL). Piperidin-4-ol (0.07 g, 1.2 eq.) was added and the reaction mixture was cooled to −60° C. T3P (propyl phosphonic anhydride) (0.40 mL, 1.2 eq.) and DIPEA (0.19 mL, 2.0 eq.) were added. Reaction mixture was stirred for 30 min. The reaction mixture was then transferred into water (50 mL) and extracted with DCM (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure (25° C., 20 mmHg) to afford crude product, which was purified by chromatography (0-3% MeOH in DCM) to obtain 0.025 g of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-1-(4-hydroxypiperidin-1-yl)prop-2-en-1-one (Yield: 10%). 1H NMR (400 MHz, CDCl3) δ, 8.75 (s, 1H), 8.58 (s, 7.93 (s, 1H), 7.08-7.11 (d, J=10.4 Hz, 1H), 6.01-6.04 (d, J=10.4 Hz, 1H), 4.02-4.14 (m, 1H), 3.98-4.01 (m, 1H), 3.78-3.85 (m, 1H), 3.47-3.52 (s, 1H), 3.32-3.38 (s, 1H), 1.96 (s, 1H), 1.83 (s, 1H), 1.27 (s, 1H), 0.90 (s, 1H); LCMS for Chemical Formula: C18H17F6N4O2 [M+H]+ 435.34 found 435.24 at RT 2.408 min.

Workup

  1. customReaction mixture
  2. extractionextracted with DCM (2×50 mL)
  3. washThe combined organic layers were washed with brine (50 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (25° C., 20 mmHg)
  7. customto afford crude product, which
  8. customwas purified by chromatography (0-3% MeOH in DCM)

Sources & evidence

ORD record
ord-07a246ab5b4a4e17b5efbead62f3d812
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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