Trifluoroacetic acid → 1-[4-(3-Benzyloxymethyl-cyclobutyl)-benzyl]-pyrrolidine

HRID 1241505Notes

Reaction equation

HRID 1241505 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]1[CH2:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:17][CH:16]=2)(O)[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCCl>[CH2:1]([O:8][CH2:9][CH:10]1[CH2:11][CH:12]([C:15]2[CH:16]=[CH:17][C:18]([CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:19][CH:20]=2)[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 112103253-Benzyloxymethyl-1-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutanol

Product 1

HCID 113366061-[4-(3-Benzyloxymethyl-cyclobutyl)-benzyl]-pyrrolidine

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirring solution of 3-benzyloxymethyl-1-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutanol (1.0 g, 2.8 mmol) in 10 mL of 1,2-dichlorethane was added triethyl silane (4.5 mL, 28.5 mmol) followed by the addition of trifluoroacetic acid (4.4 mL, 57.0 mmol). The reaction was then heated to 75 C (oil bath). After 1 hour the reaction was cooled to room temperature and then concentrated under reduced pressure. The crude material was taken up in EtOAc and washed with an aqueous solution of 1M NaOH. The layer were separated and the organic layer was dried over magnesium sulfate, filtered through a fritted funnel and concentrated under reduced pressure. Purification of this material was accomplished by flash column chromatography using a 45 g ISCO column, eluting with a gradient of 2% MeOH/CH2Cl2 w/0.1% NH4OH, through 10% MeOH/CH2Cl2 w/0.1% NH4OH. The product containing fractions were collected and concentrated to give the title compound (yield not determined due to presence of TFA) as a colorless oil and a 1:1 mixture of cis:trans isomers. Further purification of this material is not required.

Workup

  1. temperatureThe reaction was then heated to 75 C (oil bath)
  2. concentrationconcentrated under reduced pressure
  3. washwashed with an aqueous solution of 1M NaOH
  4. customThe layer were separated
  5. dry with materialthe organic layer was dried over magnesium sulfate
  6. filtrationfiltered through a fritted funnel
  7. concentrationconcentrated under reduced pressure
  8. customPurification of this material
  9. washeluting with a gradient of 2% MeOH/CH2Cl2
  10. additionThe product containing fractions
  11. customwere collected
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-afff22c49c7941868a317c20c0ce7865
Source dataset
uspto-grants-2006_10
Patent number
US07115600B2

Reaction notes

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