(R)-2-Methylpyrrolidine → HCID 178461415, compound

HRID 1988129Notes

Reaction equation

HRID 1988129 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:11][C:10](=O)[CH2:9]2)=[CH:4][CH:3]=1.[CH3:13][C@@H:14]1[CH2:18][CH2:17][CH2:16][NH:15]1>C(O)C.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:11][C@H:10]([N:15]3[CH2:16][CH2:17][CH2:18][C@H:14]3[CH3:13])[CH2:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 641544(R)-2-MethylpyrrolidineHCID 45896953-(4-Bromophenyl)cyclobutan-1-one

Product 1

HCID 178461415HCID 178461415, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To a solution of 3-(4-bromo-phenyl)-cyclobutanone (1 g, 4.44 mmol) in ethanol (20 mL) was added a solution of (R)-2-methylpyrrolidine (prepared according to the procedure that described in: R. Altenbach et al., WO 2004043458, and Y. Pu et al., Organic Process Research & Development, 9(1), 45-50, 2005) (0.75 g, 8.9 mmol) in toluene. Borane-pyridine complex (0.67 mL, 6.6 mmol) was added subsequently and stirred at ambient temperature for 16 hours. The mixture was concentrated under reduced pressure to dryness and partitioned between ethyl acetate and H2O. The organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure. Chromatography of the residue eluting with a gradient of 1-2% (9:1 MeOH:concentrated NH4OH) in dichloromethane provided the title compound (680 mg, 52%) as the faster eluting component and the product from Example 1B (76 mg, 6%) as the slower eluting component. 1H NMR (300 MHz, CD3OD) δ 1.15 (d, J=6 Hz, 3 H), 1.46 (m, 1 H), 1.77 (m, 2 H), 1.99 (m, 1 H), 2.07 (m, 2 H), 2.34 (m, 1 H), 2.58 (m, 3 H), 3.04 (m, 2 H), 3.17 (m, 1 H), 7.17 (d, J=9 Hz, 2 H), 7.41 (d, J=9 Hz, 2 H); (DCl/NH3) m/z 294 (M+H)+.

Workup

  1. customprepared
  2. additionBorane-pyridine complex (0.67 mL, 6.6 mmol) was added subsequently
  3. concentrationThe mixture was concentrated under reduced pressure to dryness
  4. custompartitioned between ethyl acetate and H2O
  5. washThe organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. washChromatography of the residue eluting with a gradient of 1-2% (9:1 MeOH:concentrated NH4OH) in dichloromethane

Sources & evidence

ORD record
ord-d151749dbce844c79fd2a67036eba2df
Source dataset
uspto-grants-2009_06
Patent number
US07553964B2

Reaction notes

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