Sodium Hydroxide → HCID 86702797, compound

HRID 1425915Notes

Reaction equation

HRID 1425915 reaction equation
[C@@H:1]12[NH:7][C@@H:4]([CH2:5][CH2:6]1)[CH:3]([C:8]([O:10]C)=[O:9])[CH:2]2[C:12]([O:14]C)=[O:13].[OH-].[Na+].[C:18](ON1C(=O)CCC1=O)([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].C(Cl)Cl.CO>O.CC(C)=O>[CH2:21]([O:20][C:18]([N:7]1[C@H:4]2[CH2:5][CH2:6][C@@H:1]1[CH:2]([C:12]([OH:14])=[O:13])[CH:3]2[C:8]([OH:10])=[O:9])=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 14798Sodium Hydroxide2×HCID 83172Benzyl succinimido carbonateHCID 21226129Dichloromethane methanolHCID 86702796HCID 86702796, compound

Product 1

HCID 86702797HCID 86702797, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

(1R,4S)-dimethyl 7-azabicyclo[2.2.1]heptane-2,3-dicarboxylate (LXIX) (2.46 g, 9.86 mmol) was suspended in water (50 mL) and aq. 1 M NaOH was added to adjust the suspension to pH 12. To this mixture was added a solution of CBz-OSu (2.70 g, 10.84 mmol) in acetone (50 mL) and the reaction mixture was stirred overnight at room temperature. An additional portion of aqueous 4 M NaOH was added to adjust the mixture to pH 14, and the mixture was stirred for another 4 hours at room temperature. The acetone was removed under vacuum and aqueous residue was washed with Et2O (×2). The aqueous layer was acidified to pH 3 using 6 M HCl and extracted with EtOAc (×3). The combined organic layers were dried over MgSO4, filtered and evaporated under vacuum. The crude product was purified by silica gel chromatography using 100% DCM then DCM/MeOH 200/1→100/1 to give (1R,4S)-7-(benzyloxycarbonyl)-7-azabicyclo[2.2.1]heptane-2,3-dicarboxylic acid (L) as a white foam (2.33 g, 7.30 mmol, 74% yield). 1H NMR (CDCl3) δ ppm 1.57 (brs, 2H), 1.75 (brs, 1H), 1.87 (brs, 1H), 3.03 (brs, 1H), 3.60 (brs, 1H), 4.67 (brs, 2H), 5.08 (brs, 2H), 7.03 (brs, 5H), 8.60 (brs, 2H); ESIMS found for C16H17NO6 m/z 342 (M+Na).

Workup

  1. stirringthe mixture was stirred for another 4 hours at room temperature
  2. customThe acetone was removed under vacuum and aqueous residue
  3. washwas washed with Et2O (×2)
  4. extractionextracted with EtOAc (×3)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated under vacuum
  8. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-9f45c1cbe0dc47ea9e442792b6f16060
Source dataset
uspto-grants-2015_01
Patent number
US08933018B2

Reaction notes

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