Water → Ethyl 2-[(1R,5R)-2,6-diazabicyclo[3.2.0]hept-6-yl]-4-methyl-1,3-thiazole-5-carboxylate

HRID 43924Notes

Reaction equation

HRID 43924 reaction equation
P(=O)(O)(O)O.[CH2:6]([O:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH2:22][C@@H:21]3[C@H:17]2[CH2:18][CH2:19][N:20]3C(OC(C)(C)C)=O)=[N:13][C:12]=1[CH3:30])=[O:10])[CH3:7].O>ClCCl>[C@@H:21]12[CH2:22][N:16]([C:14]3[S:15][C:11]([C:9]([O:8][CH2:6][CH3:7])=[O:10])=[C:12]([CH3:30])[N:13]=3)[C@@H:17]1[CH2:18][CH2:19][NH:20]2

Participants

5

Reactant 3

HCID 962WaterHCID 1004Phosphoric AcidHCID 86648822tert-Butyl (1R,5R)-6-[5-(ethoxycarbonyl)-4-methyl-1,3-thiazol-2-yl]-2,6-diazabicyclo[3.2.0]heptane-2-carboxylate

Product 1

HCID 67549645Ethyl 2-[(1R,5R)-2,6-diazabicyclo[3.2.0]hept-6-yl]-4-methyl-1,3-thiazole-5-carboxylateYield 86.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

85% phosphoric acid (0.44 mL, 3.78 mmol) was added to a solution of tert-butyl (1R,5R)-6-[5-(ethoxycarbonyl)-4-methyl-1,3-thiazol-2-yl]-2,6-diazabicyclo[3.2.0]heptane-2-carboxylate obtained in Example (236b) (278 mg, 0.76 mmol) in dichloromethane (1 mL) at room temperature, followed by stirring for two hours. Water was added to the reaction solution, and the mixture was washed with ethyl acetate. Then, a 1 N aqueous sodium hydroxide solution was added to the aqueous layer, followed by extraction with an ethyl acetate/methanol mixed solvent. The combined organic layers were dried over anhydrous magnesium sulfate and filtered. Thereafter, the solvent was evaporated under reduced pressure to obtain 175 mg of the title compound as a pale yellow oily substance (87%).

Workup

  1. washthe mixture was washed with ethyl acetate
  2. additionThen, a 1 N aqueous sodium hydroxide solution was added to the aqueous layer
  3. extractionfollowed by extraction with an ethyl acetate/methanol mixed solvent
  4. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customThereafter, the solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-eeadcb480f424924b11cd4f71d7b3c73
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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