HCID 57099902, compound → HCID 69731064, compound

HRID 1108842Notes

Reaction equation

HRID 1108842 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:11]([OH:15])[C@H:10]([C:16]([O:18]CC)=[O:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>COC(C)(C)C.[OH-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:11]([OH:15])[C@H:10]([C:16]([OH:18])=[O:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 57099902HCID 57099902, compound

Product 1

HCID 69731064HCID 69731064, compoundYield 46.3%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A mixture of 28.7 g of the compound prepared in Example 13 in 200 ml of tert-butyl methyl ether and 200 ml of 2N NaOH was stirred vigorously at room temperature for 4 hours and then at 50° C. for 20 hours. After cooling, the aqueous phase was extracted twice with 100 ml of tert-butyl methyl ether each time. The organic phases were discarded. The aqueous phase was acidified cautiously with about 70 ml of 6N HCl and extracted once with 200 ml of tert-butyl methyl ether and twice with 100 ml of tert-butyl methyl ether each time. All three organic phases were washed once with 50 ml of 10% sodium chloride solution, combined and dried over sodium sulphate. After removal of the solvent under reduced pressure (40° C./25 mbar) the brown viscous oil was dissolved in 60 ml of isopropyl ether at 60° C. and left to crystallize at -20° C. for 16 hours. The crystals were filtered off, washed with a small amount of isopropyl ether, cooled to -20° C. and dried at 40° C. for 5 hours and 25 mbar, yielding 12.0 g of (3R,4S)-4-hydroxy-azepan-1,3-dicarboxylic acid 1-tert-butyl ester of melting point 98.5-101.5° C.

Workup

  1. waitat 50° C. for 20 hours
  2. temperatureAfter cooling
  3. extractionthe aqueous phase was extracted twice with 100 ml of tert-butyl methyl ether each time
  4. extractionextracted once with 200 ml of tert-butyl methyl ether and twice with 100 ml of tert-butyl methyl ether each time
  5. washAll three organic phases were washed once with 50 ml of 10% sodium chloride solution
  6. dry with materialdried over sodium sulphate
  7. customAfter removal of the solvent under reduced pressure (40° C./25 mbar) the brown viscous oil
  8. dissolutionwas dissolved in 60 ml of isopropyl ether at 60° C.
  9. waitleft
  10. customto crystallize at -20° C. for 16 hours
  11. filtrationThe crystals were filtered off
  12. washwashed with a small amount of isopropyl ether
  13. temperaturecooled to -20° C.
  14. customdried at 40° C. for 5 hours

Sources & evidence

ORD record
ord-d0d6a7b0e27845aabca7b082ac1a5498
Source dataset
uspto-grants-2000_05
Patent number
US06069245

Reaction notes

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