Sodium hydride → [4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenylamino]-acetic acid

HRID 554023Notes

Reaction equation

HRID 554023 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([N:16]2[CH2:22][C:21]3([CH3:24])[CH2:23][CH:17]2[CH2:18][C:19]([CH3:26])([CH3:25])[CH2:20]3)=[O:15])=[CH:10][CH:9]=1)(C)(C)C.[H-].[Na+].C([O:34][C:35](=[O:38])[CH2:36]Br)(C)(C)C>CN(C=O)C>[CH3:24][C:21]12[CH2:23][CH:17]([N:16]([C:14]([C:11]3[CH:10]=[CH:9][C:8]([NH:7][CH2:36][C:35]([OH:38])=[O:34])=[CH:13][CH:12]=3)=[O:15])[CH2:22]1)[CH2:18][C:19]([CH3:25])([CH3:26])[CH2:20]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 9907515[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester

Product 1

HCID 67016360[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenylamino]-acetic acidYield 74.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester (5.0 g, 13.42 mmol) in dry DMF (75 ml) was added sodium hydride (750 mg, 33.3 mmol in 60% mineral oil) and the mixture was stirred for 30 min. Bromo-acetic acid tert-butyl ester (3.14 g, 16.11 mmol) was added and the stirring was continued for an additional 1 hr. at 50° C. The reaction was quenched by addition of water (50 ml) and extracted with diethyl ether (2×50 ml). The combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in DCM (75 ml) and TFA (40 ml) was added. The resulting mixture was stirred for 16 hrs. at room temperature and evaporated in vacuo. To the residue was added water (75 ml) and diethyl ether (25 ml) and the precipitate was filtered off, washed with diethyl ether and dried in vacuo at 50° C. affording 3.3 g (74%) of [4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]-octane-6-carbonyl)-phenylamino]-acetic acid an solid.

Workup

  1. waitthe stirring was continued for an additional 1 hr
  2. customat 50° C
  3. customThe reaction was quenched by addition of water (50 ml)
  4. extractionextracted with diethyl ether (2×50 ml)
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. dissolutionThe residue was dissolved in DCM (75 ml)
  9. additionTFA (40 ml) was added
  10. stirringThe resulting mixture was stirred for 16 hrs
  11. customat room temperature and evaporated in vacuo
  12. additionTo the residue was added water (75 ml) and diethyl ether (25 ml)
  13. filtrationthe precipitate was filtered off
  14. washwashed with diethyl ether
  15. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-3a0f687810a54e68bee63a292224c218
Source dataset
uspto-grants-2011_11
Patent number
US08048908B2

Reaction notes

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