Hydrochloric Acid → HCID 22237519, compound

HRID 1884714Notes

Reaction equation

HRID 1884714 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:43])[C:17]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[C:25]([CH3:30])[CH:24]=3)[C:20]([O:31][CH2:32][CH2:33][OH:34])=[C:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[C:37]([CH3:42])[CH:36]=3)[CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[N+]1([O-])CC[O:48]CC1.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+].Cl>C(#N)C.CCC[N+](CCC)(CCC)CCC.[O-][Ru](=O)(=O)=O.CC(O)=O.CCOC(C)=O>[F:29][C:26]1[CH:27]=[CH:28][C:23]([C:21]2[CH:22]=[C:17]([C:16](=[O:43])[NH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH:18]=[C:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[C:37]([CH3:42])[CH:36]=3)[C:20]=2[O:31][CH2:32][C:33]([OH:48])=[O:34])=[CH:24][C:25]=1[CH3:30]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 82029Methyl morpholine oxide2×HCID 22237492HCID 22237492, compoundHCID 86583661HCID 86583661, compound

Product 1

HCID 22237519HCID 22237519, compoundYield 36.6%

Reagents, catalysts & solvents 4

HCID 178419074HCID 178419074, compoundCatalyst3×HCID 176Acetic AcidSolvent2×HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-8-phenyloctyl-3,5-bis-(4-fluoro-3-methylphenyl)-4-(2-hydroxyethoxy)benzamide (320 mg, 0.546 mmol) in 5 mL acetonitrile at room temperature was added NMMO (162 mg, 1.2 mmol) and TPAP (38.3 mg, 0.109 mmol). The reaction was stirred for 2 hours then additional TPAP (38.3 mg, 0.109 mmol) was added. The reaction was stirred overnight and an additional amount of NMMO (14.7 mg, 0.109 mmol) and TPAP (19 mg, 0.546 mmol) were added. The reaction was then stirred for three more hours and aqueous sodium metabisulfite/sodium dithionite was added. The reaction was then allowed to stir for 1 hour. Then 1N HCl was added. The aqueous solution was extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4 and the solvent was removed under vacuum to give a black oil which was subjected to flash column chromatography (20% EtOAc:80% Hexanes acidified with AcOH) on silica gel that was pretreated with AcOH. There yielded 120 mg, 36.6% of the acid as a yellow oil. 1H NMR (DMSO-d6) δ 1.22-1.27 (m, 4H); 1.53 (quintet, J=6.59 Hz, 4H); 2.27-2.28 (m, 6H); 2.52 (t, J=7.69 Hz, 2H); 3.23 (quartet, J=6.59 Hz, 2H); 3.82 (s, 2H); 7.11-7.25 (m, 7H); 7.41-7.45 (m, 2H); 7.52 (dd, J=7.58 Hz, 1.87 Hz, 2H); 7.80 (s, 2H); 8.49 (t, J=5.60 Hz, 1H); 12.57 (bs, 1H); IR 3375, 2915, 2835, 1630, 1540, 1500, 1450, 1230, 1120, and 970 cm−1; mass spectrum [(−)ESI], m/z 598 [M−H]−1; Anal Calcd for C37H39F2NO4.0.17C6H2O.0.2C4H8O2.0.88C2H3O2: C, 71.16; H, 6.84; N, 2.04; Found: C, 69.55; H, 6.65; N, 2.09.

Workup

  1. stirringThe reaction was stirred overnight
  2. additionwas added
  3. stirringto stir for 1 hour
  4. extractionThe aqueous solution was extracted with EtOAc (3×)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. customthe solvent was removed under vacuum
  7. customto give a black oil which

Sources & evidence

ORD record
ord-a06adcad2b7f4dfbac2a2711f2dadf81
Source dataset
uspto-grants-2004_07
Patent number
US06765021B2

Reaction notes

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