Methanol → 1-[4-(3-Pyrrolidin-1-ylmethyl-cyclobutyl)-benzyl]-pyrrolidine

HRID 1241517Notes

Reaction equation

HRID 1241517 reaction equation
[N:1]1([CH2:6][CH:7]2[CH2:10][C:9]([C:12]3[CH:17]=[CH:16][C:15]([CH2:18][N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[CH:14][CH:13]=3)(O)[CH2:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CS(O)(=O)=O.CO>ClCCCl.[Pd]>[N:1]1([CH2:6][CH:7]2[CH2:8][CH:9]([C:12]3[CH:13]=[CH:14][C:15]([CH2:18][N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[CH:16][CH:17]=3)[CH2:10]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 219348323-Pyrrolidin-1-ylmethyl-1-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutanol

Product 1

HCID 113125751-[4-(3-Pyrrolidin-1-ylmethyl-cyclobutyl)-benzyl]-pyrrolidine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 111,2-DichloroethaneSolvent

Procedure

To a stirring solution of 3-pyrrolidin-1-ylmethyl-1-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutanol (Example 210, General procedure B, Step D) (0.10 g, 0.32 mmol) in 1,2-dichloroethane (3.2 mL) was added methanesulfonic acid (0.31 g, 3.2 mmol). The reaction was then heated to 65 □C (oil bath) for 30 minutes. The reaction was then cooled to room temperature and transferred to a Parr bottle. To this crude solution was added 5 mL of MeOH, 10% Pd/C (100 mg), and then the reaction vessel was pressurized to 45 psi with H2. After 30 min the reaction was purged with N2, filtered through a pad of celite, and concentrated under reduced pressure. Purification of this material was accomplished flash column chromatography using a 15 g ISCO column, pre-packing material on silica, eluting with a gradient of 20%–45% MeOH/CH2Cl2 with 0.1% NH4OH. The product containing fractions were collected and concentrated to give the title compound as the (0.97 mg) as the bis-methanesulfonic acid salt.

Workup

  1. temperatureThe reaction was then heated to 65 □C (oil bath) for 30 minutes
  2. customAfter 30 min the reaction was purged with N2
  3. filtrationfiltered through a pad of celite
  4. concentrationconcentrated under reduced pressure
  5. customPurification of this material
  6. washeluting with a gradient of 20%–45% MeOH/CH2Cl2 with 0.1% NH4OH
  7. additionThe product containing fractions
  8. customwere collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c562e9457da346dc8ee573409caa1a24
Source dataset
uspto-grants-2006_10
Patent number
US07115600B2

Reaction notes

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