Hydrochloric Acid → HCID 67982695, compound

HRID 1406607Notes

Reaction equation

HRID 1406607 reaction equation
Br[CH2:2][C:3]([NH:5][C@H:6]([C:8]1[CH:13]=[CH:12][C:11]([Br:14])=[CH:10][CH:9]=1)[CH3:7])=[O:4].[CH3:15][C:16]([O:27][Si](C)(C)C)([CH3:26])[CH2:17][C:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:19].C([Zn]CC)C.Cl>C(OC(C)C)(=O)C>[Br:14][C:11]1[CH:12]=[CH:13][C:8]([C@@H:6]([NH:5][C:3](=[O:4])[CH2:2][C@@:18]([OH:19])([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:17][C:16]([OH:27])([CH3:26])[CH3:15])[CH3:7])=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 151514373-Methyl-1-phenyl-3-[(trimethylsilyl)oxy]butan-1-oneHCID 68024047HCID 68024047, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 67982695HCID 67982695, compound

Reagents, catalysts & solvents 1

HCID 7915Isopropyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

A flask is charged with 1 (120.0 g, 0.366 mol), 2 (120.0 g, 0.479 mol) and NiCl2(dppe) (1.93 g, 3.66 mmol). The flask is purged with nitrogen and charged with DME (240 mL). The resultant slurry is cooled to about −20° C. and treated with diethylzinc (30 wt. % solution in toluene, 477 mL, 1.097 mol) at a rate to keep the temperature of the reaction mixture between −15 to −5° C. The reaction mixture is then stirred at −5 to 0° C. for 2 hours, treated with 6N aqueous HCl (600 mL), and stirred for 15 minutes. The reaction mixture is treated with isopropyl acetate (120 mL), stirred at 25° C. for 30 minutes, cooled to 10° C., and held at 10° C. for 30 minutes. The resultant solids are collected by filtration, and washed with water, toluene, and heptane. The solid is then dried at 70° C. for 18 hours to provide 3 as a white solid. Yield: 98.3 g, 62.1%; 97.1 wt. % purity. Diastereomeric ratio: 98.9:1.1. Melting point: 150-152° C. LC-MS: 419.8/421.8 (100%, 95%); calculated exact mass: 419.1.

Workup

  1. customThe flask is purged with nitrogen
  2. additioncharged with DME (240 mL)
  3. custombetween −15 to −5° C
  4. stirringstirred for 15 minutes
  5. stirringstirred at 25° C. for 30 minutes
  6. temperaturecooled to 10° C.
  7. waitheld at 10° C. for 30 minutes
  8. filtrationThe resultant solids are collected by filtration
  9. washwashed with water, toluene, and heptane
  10. customThe solid is then dried at 70° C. for 18 hours

Sources & evidence

ORD record
ord-a4fd57f31af1457788099c49be4aa880
Source dataset
uspto-grants-2014_12
Patent number
US08916701B2

Reaction notes

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