(R)-4-{[1-(1-Benzyl-pyrrolidin-3-yl)-cyclopropyl]-methyl-amino}-piperidine-1-carboxylic acid tert-butyl ester → Tert-butyl (R)-4-(methyl(1-(pyrrolidin-3-YL)cyclopropyl)amino)piperidine-1-carboxylate

HRID 1765113Notes

Reaction equation

HRID 1765113 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:16]2([C@@H:19]3[CH2:23][CH2:22][N:21](CC4C=CC=CC=4)[CH2:20]3)[CH2:18][CH2:17]2)[CH3:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)(=O)C.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH3:15])[C:16]2([C@@H:19]3[CH2:23][CH2:22][NH:21][CH2:20]3)[CH2:17][CH2:18]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 58593128(R)-4-{[1-(1-Benzyl-pyrrolidin-3-yl)-cyclopropyl]-methyl-amino}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 58593123Tert-butyl (R)-4-(methyl(1-(pyrrolidin-3-YL)cyclopropyl)amino)piperidine-1-carboxylateYield 87.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 1140TolueneSolvent

Procedure

(R)-4-{[1-(1-benzyl-pyrrolidin-3-yl)-cyclopropyl]-methyl-amino}-piperidine-1-carboxylic acid tert-butyl ester (14 g) was dissolved in 150 mL glacial acetic acid at room temperature in a hydrogenation flask, air was evacuated, and filled with nitrogen. To this was added 30% Pd/C (5 g), flask was mounted to Parr shaker, nitrogen was evacuated and filled with hydrogen, and the mixture was shaken under hydrogen atmosphere at 60 psi in a Parr for 18 h. Reaction mixture was diluted with toluene (300 mL), filtered through a pad of celite. The filtrate was concentrated in vacuo, residue was digested in cold 30% NaOH at 0° C. and the product was extracted with ethyl acetate. The combined ethyl acetate solution was charged with 50 g of charcoal (Darco G-60), allowed to stir for 2 h, filtered, concentrated to give pale yellow oil, which can be vacuum distilled to give a clear oil (9.6 g). 1H NMR (400 MHz, CD3OD) δ 4.04 (br s, 1H), 3.01 (dd, J=10.4 Hz and 7.6 Hz, 1H), 2.84 (dd, J=8.0 Hz and 5.2 Hz, 2H), 2.64-2.55 (m, 3H), 2.48-2.43 (m, 2H), 2.30 (s, 3H), 2.28-2.23 (m, 1H), 2.23-1.74 (m, 3H), 1.40 (s, 9H), 1.35-1.28 (m, 2H), 1.18-1.12 (m, 2H), 0.53-0.45 (m, 4H).

Workup

  1. customair was evacuated
  2. additionfilled with nitrogen
  3. additionTo this was added 30% Pd/C (5 g), flask
  4. customwas evacuated
  5. additionfilled with hydrogen
  6. customReaction mixture
  7. filtrationfiltered through a pad of celite
  8. concentrationThe filtrate was concentrated in vacuo, residue
  9. customwas digested in cold 30% NaOH at 0° C.
  10. extractionthe product was extracted with ethyl acetate
  11. additionThe combined ethyl acetate solution was charged with 50 g of charcoal (Darco G-60)
  12. stirringto stir for 2 h
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto give pale yellow oil, which
  16. distillationdistilled

Sources & evidence

ORD record
ord-8ecef23b58b54ad2bd7257dbbf52df5a
Source dataset
uspto-grants-2007_06
Patent number
US07226931B2

Reaction notes

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