Sodium Chloride → HCID 59271881, compound

HRID 1893195Notes

Reaction equation

HRID 1893195 reaction equation
Cl.[CH3:2][NH2:3].[Si:4]([O:11][CH2:12][C:13]([O:19][CH3:20])([CH3:18])[CH2:14][CH2:15][CH:16]=O)([C:7]([CH3:10])([CH3:9])[CH3:8])([CH3:6])[CH3:5].[C-:21]#[N:22].[Na+].[Na+].[Cl-].[C:26]([O:30][C:31]([O:33]C(OC(C)(C)C)=O)=O)([CH3:29])([CH3:28])[CH3:27]>O.CCOC(C)=O.O1CCOCC1>[C:26]([O:30][C:31](=[O:33])[N:3]([CH:16]([C:21]#[N:22])[CH2:15][CH2:14][C:13]([O:19][CH3:20])([CH3:18])[CH2:12][O:11][Si:4]([C:7]([CH3:10])([CH3:9])[CH3:8])([CH3:6])[CH3:5])[CH3:2])([CH3:29])([CH3:28])[CH3:27]

Participants

9

Reactant 5

HCID 5234Sodium ChlorideHCID 8929Sodium CyanideHCID 90495Di-tert-butyl dicarbonateHCID 6364545Methylamine hydrochlorideHCID 59271830HCID 59271830, compound

Product 1

HCID 59271881HCID 59271881, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
15 °C

Procedure

To a solution of methylamine hydrochloride (0.83 kg, 12.34 mol) in water (14.66 L) was added dioxane (24.43 L) and 5-{[tert-butyl(dimethyl)silyl]oxy}-4-methoxy-4-methylpentanal (crude, 2.9 kg, 11.22 mol) and NaCN (0.605 kg, 12.34 mol) over 10 minutes while maintaining the reaction temperature at 15° C. The reaction mixture was stirred overnight, then NaCl (1.7 kg) was added and the layers separated. The aqueous layer was extracted with EtOAc (2×4 L). The combined organic layers were dried over Na2SO4, filtered and concentrated to provide 5.63 kg (>100%) of crude material. To a solution of the crude residue in EtOAc (20 L) at 6° C. was added di-tert-butyldicarbonate (2.57 kg, 11.78 mol) in 1.5 L of EtOAc via additional funnel over 5 minutes. The reaction mixture was stirred at 15° C. overnight and concentrated in vacuo. Flash column chromatography eluted with 0 to 30% EtOAc in heptane provided the desired product.

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with EtOAc (2×4 L)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto provide 5.63 kg (>100%) of crude material
  7. stirringThe reaction mixture was stirred at 15° C. overnight
  8. concentrationconcentrated in vacuo
  9. washFlash column chromatography eluted with 0 to 30% EtOAc in heptane

Sources & evidence

ORD record
ord-6d5e8f161bed451885e45f645f479d45
Source dataset
uspto-grants-2013_08
Patent number
US08513234B2

Reaction notes

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