Trifluoroacetic acid → 3,9-Diazabicyclo[3.3.1]nonane-3-carboxylic acid, 9-methyl-7-oxo-, 1,1-dimethylethyl ester

HRID 33032Notes

Reaction equation

HRID 33032 reaction equation
C(OC(=O)[CH2:5][CH:6]1[CH2:11][N:10]([CH2:12]C2C=CC=CC=2)[CH2:9][CH:8]([CH2:19][C:20]([O:22]CC)=O)[N:7]1[CH3:25])C.C(O)(C(F)(F)F)=[O:28].[C:34]([O:38][K])([CH3:37])([CH3:36])[CH3:35]>CO.C1(C)C=CC=CC=1>[C:34]([O:38][C:12]([N:10]1[CH2:11][CH:6]2[N:7]([CH3:25])[CH:8]([CH2:19][C:20](=[O:22])[CH2:5]2)[CH2:9]1)=[O:28])([CH3:37])([CH3:36])[CH3:35]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 597937792,6-Diethyl 1-methyl-4-(phenylmethyl)-2,6-piperazinediacetateHCID 178418922HCID 178418922, compound

Product 1

HCID 597189763,9-Diazabicyclo[3.3.1]nonane-3-carboxylic acid, 9-methyl-7-oxo-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

(4Benzyl-6-ethoxycarbonylmethyl-1-methylpiperazin-2-yl)acetic acid ethyl ester (Patent WO 92/05174) (71.0 g, 0.196 mol) was dissolved in MeOH (400 mL). TFA (77.8 mL, 1.02 mol) was added and the flask was purged with nitrogen. Pd/C (10%, 50% moisture, 3.6 g) was added. The flask was closed and purged with hydrogen (3×). After 1 day, the mixture was filtered through celite and washed with MeOH. The solvent was removed under reduced pressure and the foamy residue (92.7 g) was dried under high vacuum. A sol. of tBuOK (117.2 g, 1.04 mol) in toluene (3.07 L) was heated to reflux. A sol. of the crude piperazine formerly obtained, dissolved in THF (300 mL), was added dropwise over 50 min.

Workup

  1. customthe flask was purged with nitrogen
  2. additionPd/C (10%, 50% moisture, 3.6 g) was added
  3. customThe flask was closed
  4. custompurged with hydrogen (3×)
  5. filtrationthe mixture was filtered through celite
  6. washwashed with MeOH
  7. customThe solvent was removed under reduced pressure
  8. dry with materialthe foamy residue (92.7 g) was dried under high vacuum

Sources & evidence

ORD record
ord-5daeb6007bb24df082b24844ac5da848
Source dataset
uspto-grants-2008_09
Patent number
US07427613B2

Reaction notes

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