Dichloroacetic Acid → HCID 59289330, compound

HRID 2191034Notes

Reaction equation

HRID 2191034 reaction equation
O[CH2:2][C@@H:3]1[C@H:7]2[O:8][C:9]([CH3:12])([CH3:11])[O:10][C@H:6]2[C@H:5]([N:13]2[C:17]3=[N:18][CH:19]=[N:20][C:21]([NH:22][C:23](=[O:30])[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[C:16]3[CH:15]=[N:14]2)[O:4]1.ClC(Cl)C(O)=O.C1CCC(N=C=NC2CCCCC2)CC1.[CH2:52]([O:54][P:55]([CH:60]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:57][CH2:58][CH3:59])=[O:56])[CH3:53]>CS(C)=O.O.CO>[C:23]([NH:22][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:13]([C@H:5]3[C@@H:6]4[O:10][C:9]([CH3:12])([CH3:11])[O:8][C@@H:7]4[C@@H:3](/[CH:2]=[CH:60]/[P:55](=[O:56])([O:57][CH2:58][CH3:59])[O:54][CH2:52][CH3:53])[O:4]3)[N:14]=[CH:15][C:16]=12)(=[O:30])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

8

Reactant 4

HCID 6597Dichloroacetic AcidHCID 10868DicyclohexylcarbodiimideHCID 10573715Diethyl(triphenylphosphoranylidene)methylphosphonateHCID 59289350HCID 59289350, compound

Product 1

HCID 59289330HCID 59289330, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Compound 22.3 (2.03 g, 4.93 mmol) in anhydrous dimethyl sulfoxide (25 mL, 0.2 M) was treated with dichloroacetic acid (400 μL, 4.93 mmol) and DCC (2.04 g, 9.67 mmol). The solution was stirred at room temperature for 2 h. [(Diethoxyphosphinyl)methylidene]triphenylphosphorane (2.0 g, 4.93 mmol, J. Org. Chem. 1996, 61, 7697-7701) was added and the mixture was stirred overnight. MeOH (25 mL) and H2O (25 mL) were added and the mixture was filtered over a plug of SiO2 and washed with MeOH (3×25 mL). The solvent was removed in vacuo and residue was suspended in CH2Cl2 and filtered over a plug of SiO2, and the solvent removed in vacuo. The residue was subjected to a column chromatography eluting with 0-100% EtOAc-hexanes, followed by 0-20% MeOH—CH2Cl2 to afford compound 22.4 (734 mg, 27% yield, E/Z ratio not determined) as a white solid (data for major isomer): 1H NMR (CDCl3, 300 MHz) 9.73 (br s, 1H), 8.71 (s, 2H), 7.91 (d, J=7.8 Hz, 2H), 7.50 (m, 1H), 7.35 (t, J=7.5 Hz, 2H), 6.89 (m, 1H), 6.15 (br s, 1H), 5.95 (m, 1H), 4.78 (m, 1H), 4.62 (m, 1H), 4.36 (m, 1H), 4.01 (m, 4H), 1.23 (m, 12H); 31P NMR (DMSO-d6, 121.4 MHz) 15.9; MS (ESI) m/z 544 [M+H+].

Workup

  1. additionwas added
  2. filtrationthe mixture was filtered over a plug of SiO2
  3. washwashed with MeOH (3×25 mL)
  4. customThe solvent was removed in vacuo and residue
  5. filtrationfiltered over a plug of SiO2
  6. customthe solvent removed in vacuo
  7. washeluting with 0-100% EtOAc-hexanes

Sources & evidence

ORD record
ord-333793ed727c42829d876d7693e85eee
Source dataset
uspto-grants-2012_12
Patent number
US08324179B2

Reaction notes

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