Hydrochloric Acid → HCID 131716331, compound

HRID 1164929Notes

Reaction equation

HRID 1164929 reaction equation
C[Si](C)(C)N[Si](C)(C)C.[K].[Br:11][CH2:12][CH2:13][CH2:14][S:15][C:16]1[CH:21]=[CH:20][C:19](CC(=[O:25])C)=[CH:18][CH:17]=1.Br[CH2:27][C:28]([O:30]C)=[O:29].Cl.[C:33]1([CH3:39])C=CC=C[CH:34]=1>C1COCC1>[Br:11][CH2:12][CH2:13][CH2:14][S:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH3:34][CH:33]([CH3:39])[C:27](=[O:25])[C:28]([OH:30])=[O:29]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 60984Methyl bromoacetateHCID 19863723HCID 19863723, compoundHCID 45051783Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, potassium salt

Product 1

HCID 131716331HCID 131716331, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of KHMDS (potassium hexamethyldisilazane) (4.96 moles) in toluene (8 L) and THF (8 L) at -78° C. under N2 was added dropwise the ketone of Step B (1.36 kg, 4.8 moles) in THF (1500 ml) over 21/2 hours. The reaction mixture was stirred 1 hour at -78° C. Methyl bromoacetate (520 ml, 5.6 moles) in THF (800 ml) was added dropwise over 1-1/2 hours. After stirring 1 hour at -78° C. the reaction mixture was poured with stirring into 16 L of HCl (lN). The organic layer was separated and the aqueous layer was further extracted with ethyl acetate (4 L). The combined organic layers were evaporated. The residue was dissolved in a mixture of THF (6 L) and EtOH (6 L), and NaOH (3 L, 2.6M) was added. After stirring 2 hours at room temperature the homogeneous reaction mixture was concentrated in vacuo to remove THF and EtOH. The aqueous residue was extracted with ethyl acetate (2×2 L). The aqueous layer was cooled in ice-water and acidified with concentrated HCl (approximately 800 ml). Extraction with ethyl acetate (1×4 L, 1×1 L), drying (Na2SO4) and evaporation afforded the title acid as a tan, oily solid, m.p. 9220 -96° C., which was used as is in Step D.

Workup

  1. stirringAfter stirring 1 hour at -78° C. the reaction mixture
  2. additionwas poured
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was further extracted with ethyl acetate (4 L)
  5. customThe combined organic layers were evaporated
  6. dissolutionThe residue was dissolved in a mixture of THF (6 L) and EtOH (6 L), and NaOH (3 L, 2.6M)
  7. additionwas added
  8. stirringAfter stirring 2 hours at room temperature the homogeneous reaction mixture
  9. concentrationwas concentrated in vacuo
  10. customto remove THF and EtOH
  11. extractionThe aqueous residue was extracted with ethyl acetate (2×2 L)
  12. temperatureThe aqueous layer was cooled in ice-water
  13. extractionExtraction with ethyl acetate (1×4 L, 1×1 L)
  14. customdrying
  15. custom(Na2SO4) and evaporation

Sources & evidence

ORD record
ord-f9ae5e3483524128851e87a558a86ad9
Source dataset
uspto-grants-1990_03
Patent number
US04906658

Reaction notes

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