1,3-Dichloroacetone → Methyl 3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]benzoate

HRID 1265592Notes

Reaction equation

HRID 1265592 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[S:11][CH:12]=[C:13]([CH2:15][O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[N:14]=2)[CH:5]=1.C[O:25][C:26](=O)[C:27]1C=CC=C(C(=S)N)C=1.Cl[CH2:38][C:39](=[O:42])[CH2:40]Cl.[C:43](=O)(O)[O-].[Na+].C[O-].[Na+]>O1CCOCC1.CO>[C:39]([O:42][C:26](=[O:25])[CH2:27][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[S:11][CH:12]=[C:13]([CH2:15][O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[N:14]=2)[CH:5]=1)([CH3:43])([CH3:40])[CH3:38].[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[S:11][CH:12]=[C:13]([CH2:15][OH:16])[N:14]=2)[CH:5]=1

Participants

9

Reactant 5

HCID 107931,3-DichloroacetoneHCID 516892Sodium BicarbonateHCID 10942334Sodium MethoxideHCID 23279244Methyl 3-carbamothioylbenzoateHCID 69687675(RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester

Product 2

HCID 69688376Methyl 3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]benzoateHCID 696884923-Oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-thiocarbamoyl-benzoic acid methyl ester [CAS-No. 106748-27-0] (7.8 g), 1,3-dichloro-2-propanone (8.4 g) and sodium bicarbonate (8.4 g) in 1,4-dioxane (180 mL) was heated to 60° C. for 24 h. The reaction mixture was cooled to 20° C. and added to a stirred solution of sodium methoxide (5.4 g) in methanol (200 mL). Stirring was continued for 0.5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was crystallized from dichloromethane/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-benzoic acid methyl ester (7.5 g) as light-brown crystals, 115-117 °C. ii.) A mixture of this material (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in ethyl acetate (50 mL) was stirred at 20 ° C. for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g).

Workup

  1. customprepared by the following sequence
  2. temperatureThe reaction mixture was cooled to 20° C.
  3. extractionthe product was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated in vacuum
  7. customThe residue was crystallized from dichloromethane/hexane

Sources & evidence

ORD record
ord-4479903dadf04097b2322e569785f724
Source dataset
uspto-grants-2003_04
Patent number
US06544985B2

Reaction notes

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