Hydrochloric Acid → 1-[1-(3,5-bis-trifluoromethyl-benzyl)-5-chloro-1H-[1,2,3]triazol-4-yl]-3-(2-chloro-phenyl)-prop-2-yn-1-ol

HRID 2251971Notes

Reaction equation

HRID 2251971 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]#[CH:9].[F:10][C:11]([F:32])([F:31])[C:12]1[CH:13]=[C:14]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)[CH2:15][N:16]1[C:20]([Cl:21])=[C:19]([CH:22]=[O:23])[N:18]=[N:17]1.O.Cl>C1COCC1.C[Mg]Br>[F:30][C:27]([F:28])([F:29])[C:25]1[CH:24]=[C:14]([CH:13]=[C:12]([C:11]([F:10])([F:32])[F:31])[CH:26]=1)[CH2:15][N:16]1[C:20]([Cl:21])=[C:19]([CH:22]([OH:23])[C:9]#[C:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[N:18]=[N:17]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 5859951-Chloro-2-ethynylbenzeneHCID 866012111-(3,5-bis-trifluoromethyl-benzyl)-5-chloro-1H-[1,2,3]triazole-4-carbaldehyde

Product 1

HCID 210877761-[1-(3,5-bis-trifluoromethyl-benzyl)-5-chloro-1H-[1,2,3]triazol-4-yl]-3-(2-chloro-phenyl)-prop-2-yn-1-ol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 178418573HCID 178418573, compoundSolvent

Procedure

Dissolve 1-chloro-2-ethynyl-benzene (22.1 g, 162 mmol) in THF (300 mL) and slowly add methyl magnesium bromide (50 mL, 3.0 M in ether). Stir solution at RT for 40 min, then add a solution of 1-(3,5-bis-trifluoromethyl-benzyl)-5-chloro-1H-[1,2,3]triazole-4-carbaldehyde (29.6 g, 82.8 mmol) in THF (160 ml). Stir resulting solution at RT for 2 h then pour into cold water (500 mL) and 1N HCl (150 mL) and extract with EtOAc (3×200 mL). Combine the organic phases and wash with saturated NaHCO3 (200 mL) and brine (200 mL) then dry, filter, and concentrate. Purify the crude material by triturating with 30% ether/hexanes to give the title compound. MS (IS) 494.0 (M+1), MS (ES−) 492.0 (M−1); 1H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.79 (s, 2H), 7.47 (dd, 1H, J=1.9, 7.3), 7.37 (dd, 1H, J=1.4, 7.9), 7.25 (dt, 1H, J=2.0, 7.3), 7.19 (dt, 1H, J=1.5, 7.3), 5.92 (d, 1H, J=6.7), 5.62 (s, 2H), 2.79 (d, 1H, J=6.4).

Workup

  1. customresulting solution at RT for 2 h
  2. extractionextract with EtOAc (3×200 mL)
  3. washCombine the organic phases and wash with saturated NaHCO3 (200 mL) and brine (200 mL)
  4. customthen dry
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the crude material
  8. customby triturating with 30% ether/hexanes

Sources & evidence

ORD record
ord-7c17a2f36a8f4430851cb2d194f86fbd
Source dataset
uspto-grants-2008_01
Patent number
US07320994B2

Reaction notes

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