2,4,5-Trichlorophenol → Ethyl 2-(4-(1-(4-(2,4,5-trichlorophenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetate

HRID 2175283Notes

Reaction equation

HRID 2175283 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][C:5]([N:7]1[C:16]2[C:11](=[C:12]([C:17]3[CH:18]=[N:19][N:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:21]=3)[CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9][CH2:8]1)=[O:6].[Cl:28][C:29]1[CH:34]=[C:33]([Cl:35])[C:32]([Cl:36])=[CH:31][C:30]=1O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[Cl:28][C:29]1[CH:34]=[C:33]([Cl:35])[C:32]([Cl:36])=[CH:31][C:30]=1[O:1][CH2:2][CH2:3][CH2:4][C:5]([N:7]1[C:16]2[C:11](=[C:12]([C:17]3[CH:18]=[N:19][N:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:21]=3)[CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9][CH2:8]1)=[O:6]

Participants

6

Reactant 4

HCID 72712,4,5-TrichlorophenolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 70983434Ethyl 2-(4-(1-(4-hydroxybutanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetate

Product 1

HCID 70982627Ethyl 2-(4-(1-(4-(2,4,5-trichlorophenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetateYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In an oven dried 1-dram vial was a mixture of ethyl 2-(4-(1-(4-hydroxybutanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetate (40 mg, 0.108 mmol), 2,4,5-trichlorophenol (34.0 mg, 0.172 mmol), triphenylphosphine (45.2 mg, 0.172 mmol) in CH2Cl2 (35.9 mL). DIAD (29.2 μL, 0.172 mmol) was added, and the reaction mixture was stirred at room temperature overnight. At the conclusion of this period, the reaction mixture was concentrated and purified by preparative HPLC (PHENOMENEX® Axia Luna column, 5μ, C18, 21.2×250 mm; 25 min gradient from 40% A:60% B to 0% A:100% B and 3 min 100% B (A=90% H2O/10% MeOH+0.1% TFA); (B=90% MeOH/10% H2O+0.1% TFA); detection at 220 nm) to afford the title compound (18.9 mg, 32% yield) as a colorless oil. LCMS, [M+H]+=550.1. 1H NMR (400 MHz, MeOD) δ 7.76 (s, 1H), 7.61 (s, 1H), 7.48 (s, 1H), 7.28-7.16 (m, 4H), 5.06 (s, 2H), 4.25 (q, J=7.1 Hz, 2H), 4.04 (br. s, 2H), 3.77 (t, J=6.8 Hz, 2H), 2.79 (t, J=7.0 Hz, 2H), 2.66 (br. s, 2H), 2.13 (dt, J=12.7, 6.4 Hz, 2H), 1.92-1.80 (m, 2H), 1.29 (t, J=7.1 Hz, 3H).

Workup

  1. customIn an oven dried 1-dram
  2. concentrationAt the conclusion of this period, the reaction mixture was concentrated
  3. custompurified by preparative HPLC (PHENOMENEX® Axia Luna column
  4. custom25 min gradient
  5. custom100% B and 3 min 100% B

Sources & evidence

ORD record
ord-291cdeb992b8469e95d820a6ccec9345
Source dataset
uspto-grants-2015_06
Patent number
US09062028B2

Reaction notes

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