Tetrahydrofuran → Triphenylphosphine Oxide

HRID 1068021Notes

Reaction equation

HRID 1068021 reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:15][CH:14]=3)=[S:9])=[CH:4][CH:3]=1.[C:30]1([P:36]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C1C[O:52]CC1.N(C(OCC)=O)=NC(OCC)=O>CO>[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH2:21][N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)[CH:17]=3)[N:12]([CH3:30])[CH:11]=2)=[S:9])=[CH:4][CH:3]=1.[C:43]1([P:36](=[O:52])([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11776Triphenylphosphine3×HCID 220568ethyl N-ethoxycarbonyliminocarbamate4×HCID 178516664HCID 178516664, compound

Product 2

HCID 13097Triphenylphosphine OxideHCID 9889538HCID 9889538, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

A flame-dried flask is charged with N-(4-chlorobenzyl)-4-hydroxy-6-(4-morpholinylmethyl)-3-quinolinecarbothioamide (0.060 g) from Preparation No. 47, triphenylphosphine (0.045 g), and freshly distilled THF (1.5 mL). To this solution is added methanol (8.00 μL) and diethyl azodicarboxylate (28.00 μL). The reaction is stirred at room temperature for 18 h. Monitoring of the reaction still shows a significant amount of starting material left. Additional PPh3 (0.025 g), methanol (5.00 μL), and diethyl azodicarboxylate (14.00 μL) are added and the reaction is stirred for 18 h. Since monitoring of the reaction still shows some starting material, 10 equivalents each of PPh3, methanol, and diethyl azodicarboxylate are added. A reasonable exotherm is seen after adding diethyl azodicarboxylate. The reaction is immediately monitored by TLC and starting material is consumed. The solvents are removed and the residue is dissolved in CH2Cl2/MeOH and adsorbed onto silica. Purification by column chromatography (eluent CH2Cl2 (1 L), 1% MeOH:CH2Cl2 (1 L), 2% MeOH:CH2Cl2 (2 L), 4% MeOH:CH2Cl2 (1 L), 7% MeOH:CH2Cl2 (1 L)) affords the title compound contaminated with triphenylphosphine oxide. These fractions are combined and concentrated and the residue is again adsorbed onto silica. Purification by a second chromatography (eluent 1:1 hexanes:ethyl acetate (1 L), 45:55 hexanes:ethyl acetate (1 L), 4:6 hexanes:ethyl acetate (1 L), 35:65 hexanes:ethyl acetate (1 L), 1:3 hexanes:ethyl acetate (1 L), 2:8 hexanes:ethyl acetate (1 L), 1:9 hexanes:ethyl acetate (1 L), 100% ethyl acetate (1 L), 2% MeOH:CH2Cl2 (1 L), 4% MeOH:CH2Cl2 (1 L)) affords the title compound as a light yellow residue. The residue is dissolved in CH2Cl2 and hexanes are added until cloudy. The solution is placed in the freezer overnight and the title compound as a solid is subsequently filtered and dried (0.020 g).

Workup

  1. customMonitoring of the reaction
  2. waitleft
  3. stirringthe reaction is stirred for 18 h
  4. customSince monitoring of the reaction
  5. additionare added
  6. customis consumed
  7. customThe solvents are removed
  8. dissolutionthe residue is dissolved in CH2Cl2/MeOH
  9. customPurification by column chromatography (eluent CH2Cl2 (1 L), 1% MeOH:CH2Cl2 (1 L), 2% MeOH:CH2Cl2 (2 L), 4% MeOH:CH2Cl2 (1 L), 7% MeOH:CH2Cl2 (1 L))

Sources & evidence

ORD record
ord-9c29d5f7a3214736860aa5341272bbeb
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Reaction notes

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