4-Chlorophenol → HCID 69339060, compound

HRID 2086198Notes

Reaction equation

HRID 2086198 reaction equation
[C:1]([O:4][CH2:5][C@H:6]([CH3:22])[CH2:7][CH:8]([NH:18][C:19](=[O:21])[CH3:20])[C:9]1[S:10][C:11]([C:14]#[C:15][CH2:16][OH:17])=[CH:12][CH:13]=1)(=[O:3])[CH3:2].[Cl:23][C:24]1[CH:29]=[CH:28][C:27](O)=[CH:26][CH:25]=1.C(OC(N=NC(OCC)=O)=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.O>[C:1]([O:4][CH2:5][C@H:6]([CH3:22])[CH2:7][CH:8]([NH:18][C:19](=[O:21])[CH3:20])[C:9]1[S:10][C:11]([C:14]#[C:15][CH2:16][O:17][C:27]2[CH:28]=[CH:29][C:24]([Cl:23])=[CH:25][CH:26]=2)=[CH:12][CH:13]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 46844-ChlorophenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 69338646HCID 69338646, compound

Product 1

HCID 69339060HCID 69339060, compoundYield 51.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(2R)-Acetylamino-2-methyl-4-[5-(3-hydroxypropynyl)thiophen-2-yl]butyl acetate (285 mg, 0.88 mmol) obtained in Example 52(a) and 4-chlorophenol (136 mg, 1.06 mmol) were dissolved in anhydrous tetrahydrofuran (5 ml), and then azodicarboxylic acid diethylester (230 mg, 1.32 mmol) and triphenylphosphine (346 mg, 1.32 mmol) were added thereto in an ice bath followed by stirring for 4 hours at room temperature. Into the reaction mixture was poured water, and the resulting solution was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=2:1-1:3) to give (2R)-acetylamino-2-methyl-4-{5-[3-(4-chlorophenoxy)propynyl]thiophen-2-yl}butyl acetate (195 mg, 51% yield) as a yellow oil. This product was dissolved in 6 ml of a mixture solvent (tetrahydrofuran:methanol:water=1:1:1), and lithium hydroxide monohydrate (370 mg, 8.82 mmol) was added thereto followed by stirring for 6 hours at 50° C. The reaction solution was poured into water, extracted with dichloromethane, and after the dichloromethane layer was dried over anhydrous sodium sulfate, the solvent was evaporated in vacuo. The residue (175 mg, 0.50 mmol) was dissolved in ethyl acetate (5 ml), and oxalic acid (45 mg, 0.50 mmol) was added thereto to precipitate crystals. The crystals were filtered off to afford the title compound (198 mg, 86% yield) as white crystals.

Workup

  1. customin an ice bath followed
  2. extractionthe resulting solution was extracted with ethyl acetate
  3. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=2:1-1:3)

Sources & evidence

ORD record
ord-131bc24e441344faad4f53e45b8ece36
Source dataset
uspto-grants-2004_04
Patent number
US06723745B2

Reaction notes

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