Sodium Bicarbonate → HCID 131733498, compound

HRID 2279961Notes

Reaction equation

HRID 2279961 reaction equation
[C:1]([Si:5]([CH3:15])([CH3:14])[O:6][CH2:7][CH2:8][C:9]1[S:10][CH:11]=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[Cl:21][C:22]1[CH:23]=[N+:24]([O-:42])[CH:25]=[C:26]([Cl:41])[C:27]=1[CH2:28][C@@H:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[C:33]([O:39][CH3:40])[CH:32]=1)[OH:30].Cl.CN(C)CCCN=C=NCC.[C:55](=O)(O)[O-:56].[Na+]>O1CCCC1.CN(C)C1C=CN=CC=1.ClCCl>[Cl:41][C:26]1[CH:25]=[N+:24]([O-:42])[CH:23]=[C:22]([Cl:21])[C:27]=1[CH2:28][C@H:29]([O:30][C:55]([C:11]1[S:10][C:9]([CH2:8][CH2:7][O:6][Si:5]([C:1]([CH3:2])([CH3:4])[CH3:3])([CH3:15])[CH3:14])=[CH:13][CH:12]=1)=[O:56])[C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[C:33]([O:39][CH3:40])[CH:32]=1

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22503634Tert-butyldimethyl(2-(thiophen-2-YL)ethoxy)silaneHCID 71092494(S)-3,5-dichloro-4-(2-(3,4-dimethoxyphenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 178418339Butyllithium

Product 1

HCID 131733498HCID 131733498, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl-dimethyl-[2-(2-thienyl)ethoxy]silane synthesized as described in example 107 step 1 (485 mg, 2 mmol) in tetrahydrofuran (7.5 mL) at −78° C. was added n-butyl lithium (0.92 mL, 2.5 M in hexanes, 2.3 mmol) dropwise. The mixture was allowed to warm to 0° C. and allowed to stir at 0° C. for 1 h. The mixture was cooled to −78° C. and then gaseous CO2 was bubbled through the mixture for 30 minutes. The mixture was quenched by the addition of saturated aqueous ammonium chloride solution (15 mL), and allowed to warm to room temperature. The mixture was extracted with ethyl acetate (3×15 mL) and the combined organic fractions were passed through a hydrophobic fit and the solvent was removed by evaporation under reduced pressure. The residue was taken up in dichloromethane (4 mL) and (1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethanol I-1/A (585 mg, 1.7 mmol), 4-dimethylaminopyridine (110 mg, 0.9 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (658 mg, 3.4 mmol) were added. The mixture was stirred at room temperature for 18 h and saturated aqueous sodium bicarbonate solution (10 mL) and dichloromethane (10 mL) were added. The layers were separated, and the organic phase was passed through a hydrophobic fit and the solvent was removed by evaporation under reduced pressure. The crude material was purified by silica gel column chromatography, eluting with 0-100% dichloromethane/10% methanol in dichloromethane, to afford the title compound (710 mg, 68%) as a brown oil.

Workup

  1. temperatureThe mixture was cooled to −78° C.
  2. customgaseous CO2 was bubbled through the mixture for 30 minutes
  3. customThe mixture was quenched by the addition of saturated aqueous ammonium chloride solution (15 mL)
  4. temperatureto warm to room temperature
  5. extractionThe mixture was extracted with ethyl acetate (3×15 mL)
  6. customthe solvent was removed by evaporation under reduced pressure
  7. stirringThe mixture was stirred at room temperature for 18 h
  8. customThe layers were separated
  9. customthe solvent was removed by evaporation under reduced pressure
  10. customThe crude material was purified by silica gel column chromatography
  11. washeluting with 0-100% dichloromethane/10% methanol in dichloromethane

Sources & evidence

ORD record
ord-20be4a3e7bb24819b2d5995feadaf864
Source dataset
uspto-grants-2015_09
Patent number
US09133185B2

Reaction notes

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