Sodium Hydroxide → HCID 178485999, compound

HRID 1063631Notes

Reaction equation

HRID 1063631 reaction equation
[CH2:1]([O:8][C:9](=[O:19])[N:10]([C@H:12]1[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14][CH2:13]1)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:24][C:25](=[O:28])[CH2:26]Br)(C)(C)C.[OH-].[Na+]>C1(C)C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([O:8][C:9]([N:10]([CH3:11])[C@H:12]1[CH2:17][CH2:16][C@H:15]([O:18][CH2:26][C:25]([OH:28])=[O:24])[CH2:14][CH2:13]1)=[O:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetate2×HCID 178485998HCID 178485998, compound

Product 1

HCID 178485999HCID 178485999, compoundYield 99.4%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalyst2×HCID 1140TolueneSolvent

Procedure

To a suspension of 15.0 g (57 mmol) of trans-(4-hydroxy-cyclohexyl)-methyl-carbamic acid benzyl ester in 230 mL of toluene were added 16.8 mL (114 mmol, 2 eq) of bromo-acetic acid tert-butyl ester and 1.93 g (5.7 mmol, 0.1 eq) of tetra-n-butylammonium hydrogensulfate and 400 mL of 50% aqueous NaOH. The mixture was stirred at RT for 4 h, additional 1.93 g (5.7 mmol, 0.1 eq) of tetra-n-butylammonium hydrogensulfate and 4.2 mL of bromo-acetic acid tert-butyl ester were added and stirring was continued over night. The solution was concentrated and acidified by addition of 400 mL of 37% HCl. The solution was extracted with EtOAc, the organic phase was washed with brine and dried over Na2SO4. The solvent was removed to yield 18.2 g (quantitative) of trans-[4-(benzyloxycarbonyl-methyl-amino)-cyclohexyloxy]-acetic acid as white solid, MS: 320 (M−H)−.

Workup

  1. stirringstirring
  2. waitwas continued over night
  3. concentrationThe solution was concentrated
  4. additionacidified by addition of 400 mL of 37% HCl
  5. extractionThe solution was extracted with EtOAc
  6. washthe organic phase was washed with brine
  7. dry with materialdried over Na2SO4
  8. customThe solvent was removed

Sources & evidence

ORD record
ord-9aa74da2d9b54171a191403721f8b792
Source dataset
uspto-grants-2005_11
Patent number
US06965048B2

Reaction notes

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