Piperidin-4-ol → HCID 71494897, compound

HRID 1465873Notes

Reaction equation

HRID 1465873 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

Procedure

A 50-mL, 3-necked, round-bottomed flask was charged with a solution of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.20 g) in CH2Cl2 (10 mL). Piperidin-4-ol (0.07 g, 1.2 eq.) was added and the solution was cooled to −60° C. for the addition of T3P (propyl phosphonic anhydride) (0.40 mL, 1.2 eq.) and DIPEA (0.19 mL, 2.0 eq.). The reaction mixture was stirred for 30 min before being poured into water (50 mL) and extracted with CH2Cl2 (2×50 mL). The combined organic layers were washed with aqueous saturated brine (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure (25° C., 20 mmHg). Purification by column chromatography using silica 60/120 and MeOH:CH2Cl2 as mobile phase. (desired compound started eluting using 3.0% MeOH/CH2Cl2) afforded 0.025 g (yield: 10%) 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. 1H NMR (400 MHz, CDCl3) δ, 8.75 (s, 1H), 8.58 (s, 2H), 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 (RT 2.408 min, purity: 89.6%).

Workup

  1. extractionextracted with CH2Cl2 (2×50 mL)
  2. washThe combined organic layers were washed with aqueous saturated brine (50 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure (25° C., 20 mmHg)
  6. customPurification by column chromatography
  7. wash(desired compound started eluting using 3.0% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-951cf86b8f72450b9b161c861983e67d
Source dataset
uspto-grants-2015_04
Patent number
US08999996B2

Reaction notes

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