alpha-Chlorohydrin, (+)- → 3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(5-ethyl-4-p-tolyl-thiophen-2-yl)-propan-1-one

HRID 552294Notes

Reaction equation

HRID 552294 reaction equation
[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:20])[CH2:9][CH2:10][C:11]2[CH:16]=[C:15]([CH3:17])[C:14]([OH:18])=[C:13]([CH3:19])[CH:12]=2)=[CH:5][C:4]=1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)[CH3:2].Cl[CH2:29][C@@H:30]([OH:33])[CH2:31][OH:32]>C(O)C.[OH-].[Na+].O>[OH:33][C@@H:30]([CH2:31][OH:32])[CH2:29][O:18][C:14]1[C:15]([CH3:17])=[CH:16][C:11]([CH2:10][CH2:9][C:8]([C:6]2[S:7][C:3]([CH2:1][CH3:2])=[C:4]([C:21]3[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=3)[CH:5]=2)=[O:20])=[CH:12][C:13]=1[CH3:19]

Participants

6

Reactant 2

HCID 148904alpha-Chlorohydrin, (+)-2×HCID 592489921-(5-Ethyl-4-p-tolyl-thiophen-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)-propan-1-one

Product 1

HCID 592489823-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(5-ethyl-4-p-tolyl-thiophen-2-yl)-propan-1-one

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 1-(5-ethyl-4-p-tolyl-thiophen-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)-propan-1-one (47 mg, 0.125 mmol) in ethanol (2 mL) and 3 N aq. NaOH (0.5 mL) is treated with (S)-3-chloro-propane-1,2-diol (90 μL) and the mixture is stirred at 60° C. for 20 h. Another portion of (S)-3-chloro-propane-1,2-diol (60 μL) is added and stirring is continued at 60° C. for 5 days. The reaction mixture is diluted with water and extracted with DCM. The solvent of the organic extract is evaporated and the crude product is purified on prep. TLC plates with heptane:EA 2:1 to give 3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(5-ethyl-4-p-tolyl-thiophen-2-yl)-propan-1-one (6 mg) as a colourless resin; LC-MS: tR=1.05 min, [M+1]+=453.25; 1H NMR (CDCl3): δ 7.56 (s, 1H), 7.30-7.21 (m, 4H), 6.88 (s, 2H), 4.11-4.05 (m, 1H), 3.87-3.80 (m, 4H), 3.18-3.11 (m, 2H), 2.98-2.85 (m, 4H), 2.39 (s, 3H), 2.25 (s, 6H), 1.29 (t, J=7.6 Hz, 3H).

Workup

  1. stirringstirring
  2. waitis continued at 60° C. for 5 days
  3. extractionextracted with DCM
  4. extractionThe solvent of the organic extract
  5. customis evaporated
  6. customthe crude product is purified on prep

Sources & evidence

ORD record
ord-a6c215c5ee474559b8c66a2b2725d771
Source dataset
uspto-grants-2011_05
Patent number
US07951794B2

Reaction notes

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