Dodecylamine → N-Dodecyl-3-bromo-4-(2-hydroxyethoxy)-5-(3-chloro-4-fluorophenyl)benzamide

HRID 1884706Notes

Reaction equation

HRID 1884706 reaction equation
[CH2:1]([NH2:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[Li]CCCC.C([O:21][C:22](=O)[C:23]1[CH:28]=[C:27]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[C:31]([Cl:36])[CH:30]=2)[C:26]([O:37][CH2:38][CH2:39][OH:40])=[C:25]([Br:41])[CH:24]=1)C>C1COCC1.O.Cl>[CH2:1]([NH:13][C:22](=[O:21])[C:23]1[CH:28]=[C:27]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[C:31]([Cl:36])[CH:30]=2)[C:26]([O:37][CH2:38][CH2:39][OH:40])=[C:25]([Br:41])[CH:24]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]

Participants

7

Reactant 3

HCID 13583DodecylamineHCID 541260063-Bromo-4-(2-hydroxyethoxy)-5-(3-chloro4-fluorophenyl)benzoic acid ethyl esterHCID 178418339Butyllithium

Product 1

HCID 22237647N-Dodecyl-3-bromo-4-(2-hydroxyethoxy)-5-(3-chloro-4-fluorophenyl)benzamideYield 58%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Into a flamed dried round bottom flask charged with n-dodecylamine (586 mg, 3.16 mmol) in 7 mL THF at −20° C. was added n-BuLi (1.8 mL, 3.6 mmol) as a solution in hexanes. After the addition, the reaction was warmed up to room temperature and stirred for one-half hour. Then the solution was cooled to −20° C. and was added to a solution of 3-bromo-4-(2-hydroxyethoxy)-5-(3-chloro-4-fluorophenyl)benzoic acid ethyl ester (400 mg, 0.957 mmol) in 8 mL THF that had been previously cooled to −40° C. The resulting mixture was stirred at 40° C. for 5 min after which point the reaction mixture was allowed to warm up to room temperature. The reaction was diluted with water and 2N HCl then extracted with EtOAc three times. The combined organic extracts were washed with sat NaHCO3 then dried over Na2SO4. After filtering and removal of solvent in vacuo, there yielded a yellow oil that was subjected to column chromatography on silica gel (10% EtOAc:90% Hexanes followed by 25% EtOAc:75% Hexanes). There resulted 300 mg, 58% of the amide as a yellow oil. 1H NMR (CDCl3) 0.868 (t, J=8.13 Hz, t); 1.20-1.40 (m, 18H); 1.48-1.67 (m, 2H); 1.895-2.00 (bs, 1H); 3.427 (q, J=8.13 Hz, 2H); 3.636-7.71 (m, 4H); 6.014 (m, 1H); 7.20-7.24 (m, 1H); 7.40-7.454 (m, 1H); 7.586-7.668 (m, 2H); 7.868 (d, J=2.04 Hz, 1H).

Workup

  1. customInto a flamed dried round bottom flask
  2. additionAfter the addition
  3. temperatureThen the solution was cooled to −20° C.
  4. temperaturehad been previously cooled to −40° C
  5. stirringThe resulting mixture was stirred at 40° C. for 5 min after which
  6. temperatureto warm up to room temperature
  7. extractionthen extracted with EtOAc three times
  8. washThe combined organic extracts were washed with sat NaHCO3
  9. dry with materialthen dried over Na2SO4
  10. filtrationAfter filtering
  11. customremoval of solvent in vacuo, there
  12. customyielded a yellow oil that

Sources & evidence

ORD record
ord-4cccb2e5ebab463aa9a37ef87391ce44
Source dataset
uspto-grants-2004_07
Patent number
US06765021B2

Reaction notes

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