Acetic Acid → {4-[(S)-3-(2-Methyl-pyrrolidin-1-yl)-cyclopentyl]-phenyl}-carbamic acid benzyl ester

HRID 1027400Notes

Reaction equation

HRID 1027400 reaction equation
[CH2:1]([O:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C@H:17]2[CH2:21][CH2:20][C:19](=O)[CH2:18]2)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][CH:25]1[CH2:29][CH2:28][CH2:27][NH:26]1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C@H:17]2[CH2:21][CH2:20][CH:19]([N:26]3[CH2:27][CH2:28][CH2:29][CH:25]3[CH3:24])[CH2:18]2)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 130032-MethylpyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 67479216[4-((S)-3-Oxo-cyclopentyl)-phenyl]-carbamic acid benzyl ester

Product 1

HCID 67479179{4-[(S)-3-(2-Methyl-pyrrolidin-1-yl)-cyclopentyl]-phenyl}-carbamic acid benzyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent3×HCID 6344DichloromethaneSolvent

Procedure

[4-((S)-3-Oxo-cyclopentyl)-phenyl]-carbamic acid benzyl ester (618 mg, 2 mmol, 1 equiv.) was dissolved in DCE (20 mL). To this solution was transferred a solution of 2-methylpyrrolidine (212 mg, 2.5 mmol, 1.25 equiv.) in 3 mL of DCE, followed by acetic acid (360 mg, 6 mmol, 3 equiv) in DCE (2 mL), then by addition of powder NaBH(OAc)3 (1.27 g, 6 mmol, 3 equiv.) in one portion under N2 at r.t. The yellowish milky solution was stirred at r.t. 24 h. The reaction was diluted with DCM (20 mL) and quenched with 10 mL of NaHCO3. The two layers were separated, and the aqueous layer was extracted with DCM (10 mL×2). The combined DCM extracts were washed with sodium bicarbonate (10 mL), brine (15 mL), dried (anhydrous potassium carbonate), filtered, and concentrated. The residue, a thick oil, was dissolved in DCM, and purified on a silica gel column to afford 0.61 g (81%) of the title compound.

Workup

  1. custom24 h
  2. customquenched with 10 mL of NaHCO3
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with DCM (10 mL×2)
  5. washThe combined DCM extracts were washed with sodium bicarbonate (10 mL), brine (15 mL)
  6. dry with materialdried (anhydrous potassium carbonate)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue, a thick oil, was dissolved in DCM
  10. custompurified on a silica gel column

Sources & evidence

ORD record
ord-b8472518dd9942228236354839faa921
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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