Triethylamine → Ethyl 1-Boc-3-pyrrolidinecarboxylate

HRID 532976Notes

Reaction equation

HRID 532976 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16](N(CC)CC)[CH3:17].ClC(OCC)=O.CN(C1C=CC=CN=1)C>O1CCCC1.C(O)C>[N:8]1([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:12][CH2:11][CH:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:9]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 218852-DimethylaminopyridineHCID 27605291-((Tert-butoxy)carbonyl)pyrrolidine-3-carboxylic acid

Product 1

HCID 4192972Ethyl 1-Boc-3-pyrrolidinecarboxylateYield 82.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-(tert-butoxycarbonyl)pyrrolidine-3-carboxylic acid (28) (1.0 g, 0.0046 mol) and triethylamine (0.78 mL, 0.0056 mol) were dissolved in 20 mL tetrahydrofuran and cooled over ice water. Ethyl chloroformate (0.48 mL, 0.0051 mol) was added dropwise at 0-5° C. and the reaction was stirred for 30 minutes. A catalytic amount of dimethylaminopyridine was added followed by 5 mL ethanol and the mixture was warmed to room temperature and stirred for 1 hour. The mixture was concentrated and partitioned between water (50 mL) and ethyl acetate (1×100 mL). The aqueous layer was extracted with an additional 50 mL ethyl acetate. The combined organics were washed with 1×50 mL water, 1×25 mL saturated sodium chloride, and dried over Na2SO4. The dried organics were evaporated to an oil. The residue was chromatographed with 10 g silica gel, 20% ethyl acetate/hexanes, to obtain 0.92 g of clear colorless oil. MS (ESI) m/z 282 [M+K]+. NMR (CDCl3) δ 1.25-1.31 (t, 3H), 1.49 (s, 9H), 1.57 (s, 2H), 3.01-3.07 (m, 1H), 3.30-3.36 (m, 1H), 3.47-3.65 (m, 3H), 4.13-4.20 (m, 2H).

Workup

  1. stirringstirred for 1 hour
  2. concentrationThe mixture was concentrated
  3. custompartitioned between water (50 mL) and ethyl acetate (1×100 mL)
  4. extractionThe aqueous layer was extracted with an additional 50 mL ethyl acetate
  5. washThe combined organics were washed with 1×50 mL water, 1×25 mL saturated sodium chloride
  6. dry with materialdried over Na2SO4
  7. customThe dried organics were evaporated to an oil
  8. customThe residue was chromatographed with 10 g silica gel, 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-54a8c2c5503447c18c85e3017d6e7097
Source dataset
uspto-grants-2014_10
Patent number
US08853219B2

Reaction notes

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