Sodium Hydroxide → HCID 69110427, compound

HRID 1359463Notes

Reaction equation

HRID 1359463 reaction equation
[C:1]([C:8]1([C:15]([O:17]C(C)(C)C)=[O:16])[NH:12]C(=O)N[C:9]1=O)(OC(C)(C)C)=O.[OH-].[Na+].O1[CH2:29][CH2:28][O:27][CH2:26]C1.[C:30](Cl)([O:32][CH2:33][CH:34]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40]2[C:35]1=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:31]>COCCOC>[C:30]([CH:9]1[CH2:41][CH:46]([C:34]2[CH:35]=[CH:36][CH:29]=[C:28]([O:27][CH3:26])[CH:33]=2)[CH2:45][CH2:1][C:8]1([NH2:12])[C:15]([OH:17])=[O:16])([O:32][CH2:33][CH:34]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40]2[C:35]1=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:31]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 343679-Fluorenylmethyl chloroformateHCID 22139635HCID 22139635, compound

Product 1

HCID 69110427HCID 69110427, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

The bis-Boc hydantoin (2.30 g, 4.84 mmol) was dissolved in DME (80 mL) to give a clear solution. To this solution was added 1N NaOH (44 mL, 44 mmol) and the reaction was stirred overnight at room temperature, giving a slightly cloudy mixture. HPLC showed completion of the reaction. The reaction mixture was concentrated under reduced pressure to remove DME and extracted with Et2O. Without purification, the resulting aqueous layer containing 1-amino-4-(3-methoxyphenyl)cyclohexane carboxylic acid (3-MeOAPC) was treated with 6N HCl to adjust the pH to 11-12. To this solution (˜40 mL) were added dioxane (80 mL) and Fmoc-Cl (1.73 g, 6.76 mmol, 1.4 equiv) and the reaction was stirred overnight at room temperature. The reaction mixture was then concentrated under reduced pressure to remove DME, neutralized with 3N HCl and extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4 and concentrated. The crude product was purified by flash chromatography on silica gel (CH2Cl2/MeOH, 98/2→90/10) to give the pure product as a white solid (1.98 g, 87% yield from bis-Boc hydantoin). 1H NMR (DMSO-d6), 7.88 (d, 2H), 7.75 (d, 2H), 7.40 (td, 2H), 7.30 (td, 2H), 7.21 (m, 1H), 6.71-6.80 (m, 3H), 3.72 (s, 3H); MS (electrospray) m/e 494 (M+Na), Calcd for C29H29NO5, 471.

Workup

  1. customto give a clear solution
  2. customgiving a slightly cloudy mixture
  3. customcompletion of the reaction
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customto remove DME
  6. extractionextracted with Et2O
  7. customWithout purification
  8. additionthe resulting aqueous layer containing 1-amino-4-(3-methoxyphenyl)cyclohexane carboxylic acid (3-MeOAPC)
  9. additionwas treated with 6N HCl
  10. stirringthe reaction was stirred overnight at room temperature
  11. concentrationThe reaction mixture was then concentrated under reduced pressure
  12. customto remove DME
  13. extractionextracted with EtOAc
  14. washThe combined organic extracts were washed with brine
  15. dry with materialdried over anhydrous Na2SO4
  16. concentrationconcentrated
  17. customThe crude product was purified by flash chromatography on silica gel (CH2Cl2/MeOH, 98/2→90/10)

Sources & evidence

ORD record
ord-027d2e7d78e146c7a4afecd64eaf48d4
Source dataset
uspto-grants-2003_07
Patent number
US06600015B2

Reaction notes

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