2-Trimethylsilylthiazole → HCID 68840249, compound

HRID 660728Notes

Reaction equation

HRID 660728 reaction equation
[Li]CCCC.C[Si](C)(C)[C:8]1[S:9][CH:10]=[CH:11][N:12]=1.[CH2:15]([O:22][C:23]1[CH:28]=[C:27](I)[CH:26]=[CH:25][C:24]=1[N:30]1[S:34](=[O:36])(=[O:35])[N:33]([CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C:32](=[O:43])[CH2:31]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CCOCC.C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:15]([O:22][C:23]1[CH:28]=[C:27]([C:8]2[S:9][CH:10]=[CH:11][N:12]=2)[CH:26]=[CH:25][C:24]=1[N:30]1[S:34](=[O:35])(=[O:36])[N:33]([CH2:37][CH2:38][Si:39]([CH3:41])([CH3:40])[CH3:42])[C:32](=[O:43])[CH2:31]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 3

HCID 5884532-TrimethylsilylthiazoleHCID 667569375-(2-Benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-oneHCID 178418339Butyllithium

Product 1

HCID 68840249HCID 68840249, compound

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of n-BuLi (2.5M in hexane, 0.44 mL, 1.1 mmol) in Et2O (1 mL) at −78° C. is added 2-(trimethylsilyl)thiazole (0.16 mL, 1.0 mmol) and the reaction mixture is stirred at −78° C. for 30 min. Zinc chloride (1.0 M in Et2O1 3.0 mL, 3.0 mmol) is added and the mixture is warmed to RT over 30 min. The ether is removed under reduced pressure then a solution of 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one (250 mg, 0.46 mmol) and Pd(PPh3)4 (55 mg, 0.046 mmol) in THF (1 mL) is added. The yellow solution is stirred at RT for 1 h then is heated at reflux for 2 h. The mixture is quenched with 1N HCl, extracted with EtOAc, washed with brine, dried over MgSO4 and concentrated. The residue is purified by chromatography using EtOAc/hexane as eluent to afford the title compound as a yellow solid: 1H NMR (CDCl3) δ 0.01 (s, 9H), 0.83 (m, 2H), 3.51 (m, 2H), 4.33 (s, 2H), 5.13 (s, 2H), 7.27-7.37 (m, 6H) 7.48 (m, 2H), 7.73 (br s, 1H), 7.82 (d, J=4 Hz, 1H); (M+1)+=502.

Workup

  1. temperaturethe mixture is warmed to RT over 30 min
  2. customThe ether is removed under reduced pressure
  3. stirringThe yellow solution is stirred at RT for 1 h
  4. temperaturethen is heated
  5. temperatureat reflux for 2 h
  6. customThe mixture is quenched with 1N HCl
  7. extractionextracted with EtOAc
  8. washwashed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe residue is purified by chromatography

Sources & evidence

ORD record
ord-300b20a4a9cd4a79bc267f5d455b5f93
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Reaction notes

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