1,2-Dichloroethane → HCID 22052248, compound

HRID 1831612Notes

Reaction equation

HRID 1831612 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH:16](NCCOCC)[CH3:17])=[CH:6][CH:5]=1)[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(=O)(O)[O-].[Na+]>ClCCl.O>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][CH3:17])=[CH:6][CH:5]=1)[CH3:2]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 22052251HCID 22052251, compound

Product 1

HCID 22052248HCID 22052248, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 13.5 mg [1-(4′-ethoxy-biphenyl-2-yl)-ethyl]-(2-ethoxy-ethyl)-amine (43.1 μmol, 1.00 equiv), 10.5 mg 4′-(trifluoromethyl)phenylacetic acid (51.7 μmol, 1.20 equiv), 9.9 mg EDC (51.7 μmol, 1.20 equiv), and 1.0 mg HOBT (7.4 μmol, 0.18 equiv) dissolved in 2.0 mL dichloromethane was stirred at room temperature for 2 h. To the reaction solution was added 5 mL aqueous saturated sodium bicarbonate solution. The aqueous layer was diluted with water to 15 mL and extracted with dichloromethane (2×20 mL). The combined organic separations were dried over magnesium sulfate, filtered, and concentrated in vacuo to yield a yellow oil. The crude product was adsorbed onto a column of silica gel (3.5 cm o.d.×10 cm h) and eluted with 17% to 25% ethyl acetate gradient in hexane. Fractions containing product were combined and concentrated in vacuo to afford 12.8 mg purified product as a colorless oil. 1H NMR (d6-DMSO; T=140° C.) δ 1.04 (t, 3H, J=6.8 Hz), 1.34 (t, 3H, J=6.8 Hz), 1.44 (d, 3H, J=7.2 Hz), 3.00–3.06 (m, 1H), 3.17–3.36 (m, 6H), 3.49 (d, 1H, J=16.0 Hz), 4.07 (q, 2H, J=6.8 Hz), 5.43 (q, 1H, J=7.2 Hz), 6.92–6.96 (m, 2H), 7.13–7.18 (m, 3H), 7.22–7.26 (m, 2H), 7.34 (ddd, 1H, J1=1.2 Hz, J2=7.6 Hz, J3=8.4 Hz), 7.39 (ddd, 1H, J1=2.0 Hz, J2=7.6 Hz, J3=9.2 Hz), 7.53–7.59 (m, 3H) ppm. At room temperature, compound exists as a mixture of cis/trans amide rotamers in ca. 2:1 ratio as determined by integration of characteristic 1H NMR signals (CDCl3; T=25° C.), δmajor 5.19 (q, 2.1H, J=7.2 Hz) and δminor 5.89 (q, 1.0H, J=7.6 Hz) ppm. MS (ESI, positive mode) 500.1 [MH]+

Workup

  1. extractionextracted with dichloromethane (2×20 mL)
  2. dry with materialThe combined organic separations were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto yield a yellow oil
  6. washeluted with 17% to 25% ethyl acetate gradient in hexane
  7. additionFractions containing product
  8. concentrationconcentrated in vacuo
  9. customto afford 12.8 mg
  10. custompurified product as a colorless oil
  11. additionAt room temperature, compound exists as a mixture of cis/trans amide rotamers in ca. 2:1 ratio
  12. customas determined by integration of characteristic 1H NMR signals (CDCl3; T=25° C.), δmajor 5.19 (q, 2.1H, J=7.2 Hz) and δminor 5.89 (q, 1.0H, J=7.6 Hz) ppm

Sources & evidence

ORD record
ord-9668501a0bd54886848378e9862de00a
Source dataset
uspto-grants-2006_06
Patent number
US07067662B2

Reaction notes

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