Triethylamine → (R)-1-Boc-2-methylpyrrolidine

HRID 1296178Notes

Reaction equation

HRID 1296178 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13]I)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[H][H]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH3:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 11312942(S)-2-Iodomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester2×HCID 178418361HCID 178418361, compound

Product 1

HCID 1519407(R)-1-Boc-2-methylpyrrolidineYield 86.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A heterogenous reaction mixture of 2-(S)-iodomethyl-pyrrolidine-1-carboxylic acid tert butyl ester (compound (4) obtained from above, 25 g, 0.08 mol), triethylamine (11.2 mL, 8.12 g, 0.08 mol) in methanol (250 mL) and 5% palladium on carbon (2.5 g, 10 wt %, Pd/C) was allowed to react at room temperature under a blanket of hydrogen gas overnight and until HPLC showed less than 1% starting material (˜7 hours). The reaction mixture was filtered and the filtrate was concentrated to a residue. The residue was dissolved in distilled water (100 mL) and ethyl acetate (100 mL). The organic layer was separated and the aqueous layer was re-extracted with ethyl acetate (2×50 mL). The combined organic layer was washed with 1 M aqueous H3PO4 (2×100 mL) followed by saturated NaHCO3 (233 100 mL), dried over MgSO4, filtered, and concentrated to leave an oily residual product (12.78 g, 85.9% yield). 1H NMR (CDCl3): δ 1.16 (d, 3H, CH3), 1.47 (s, 9H, 3×CH3), 1.50–1.82 (m, 2H, CH2), 1.84–2.03 (m, 2H, CH2 ), 3.34 (m, 2H, CH2) and 3.86 (m, 1H, CH); [M+H]+ at m/z 186.

Workup

  1. custommaterial (˜7 hours)
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated to a residue
  4. dissolutionThe residue was dissolved in distilled water (100 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was re-extracted with ethyl acetate (2×50 mL)
  7. washThe combined organic layer was washed with 1 M aqueous H3PO4 (2×100 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-cde337c3e7bd4aad8fc13b83d6812a19
Source dataset
uspto-grants-2007_07
Patent number
US07244852B2

Reaction notes

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