Hydrochloric Acid → (3-Bromo-3'-chloro-5-dodecylcarbamoyl-4'-fluoro-biphenyl-2-yloxy)acetic acid

HRID 324083Notes

Reaction equation

HRID 324083 reaction equation
[CH2:1]([NH:13][C:14](=[O:34])[C:15]1[CH:20]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([Cl:28])[CH:22]=2)[C:18]([O:29][CH2:30][CH2:31][OH:32])=[C:17]([Br:33])[CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C[N+]1([O-])CC[O:39]CC1.S(=O)(O)[O-].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+].Cl>C(Cl)Cl.CCC[N+](CCC)(CCC)CCC.[O-][Ru](=O)(=O)=O.C(O)=O.CCOC(C)=O.O.CC#N>[Br:33][C:17]1[C:18]([O:29][CH2:30][C:31]([OH:39])=[O:32])=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([Cl:28])[CH:22]=2)[CH:20]=[C:15]([C:14](=[O:34])[NH:13][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH:16]=1

Participants

11

Reactant 4

HCID 313Hydrochloric AcidHCID 82029Methyl morpholine oxide2×HCID 22237647N-Dodecyl-3-bromo-4-(2-hydroxyethoxy)-5-(3-chloro-4-fluorophenyl)benzamideHCID 86583660Sodium bisulfite sodium dithionite

Product 1

HCID 22237422(3-Bromo-3'-chloro-5-dodecylcarbamoyl-4'-fluoro-biphenyl-2-yloxy)acetic acid

Reagents, catalysts & solvents 6

HCID 178419074HCID 178419074, compoundCatalyst2×HCID 284Formic AcidSolventHCID 962WaterSolvent3×HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-dodecyl-3-bromo-4-(2-hydroxyethoxy)-5-(3-chloro-4-fluorophenyl)benzamide (340 mg, 0.61 mmol) in 5 mL CH2Cl2 was added NMMO.H2O (165 mg, 1.22 mmol) and TPAP (22 mg, 0.061 mmol). The reaction mixture was stirred overnight and 2 mL CH3CN and 50 mg, 0.14 mmol TPAP were added. The reaction was stirred for ca 7 hours then 90 mg, 0.665 mmol NMMO.H2O was added and the reaction was stirred overnight. The reaction was worked up by adding H2O and a mixture of sodium bisulfite/sodium dithionite and was stirred for 4 hours. The now grayish mixture was acidified with 2N HCl and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4 followed by filtration and removal of solvent in vacuo. There yielded a black semisolid that was subjected to column chromatography (40% EtOAc:60% Hexanes) on silica gel pretreated with HCOOH. Yield of the acid is 130 mg, 37% as a dark yellowish brown oil. 1H NMR (DMSO-d6) δ0.84 (t, J=6.81 Hz, 3H); 1.22-1.27 (m, 18H); 1.50 (t, J=6.37 Hz, 2H); 3.23 (q, J=6.81 Hz, 2H); 4.19 (s, 2H); 7.51 (t, J=8.57 Hz, 1H); 7.57-7.61 (m, 1H); 7.81 (dd, J=7.25 Hz, 2.20 Hz, 1H); 7.85 (d, J=2.2 Hz, 1H); 8.10 (d, J=2.20 Hz, 1H); 8.56 (t, J=5.49 Hz, 1H); 12.75 (bs, 1H); IR 3370, 2930, 1730, 1635, 1400, 1225, 1150, and 700 cm−1; mass spectrum [(+)APCI], m/z 570 [M+H]+; Anal. Calcd. for C27H34BrClFNO4: C, 56.80; H, 6.00; N, 2.45, Found: C, 54.30; H, 5.73; N, 2.18.

Workup

  1. stirringThe reaction was stirred for ca 7 hours
  2. stirringthe reaction was stirred overnight
  3. stirringwas stirred for 4 hours
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfollowed by filtration and removal of solvent in vacuo
  7. customThere yielded a black semisolid that

Sources & evidence

ORD record
ord-adacf61ff2d247858183829f84c2279a
Source dataset
uspto-grants-2001_04
Patent number
US06214877B1

Reaction notes

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