Toluene → Benzyloxycarbonyl-L-proline

HRID 21765

Reaction equation

HRID 21765 reaction equation
[NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].Cl[C:10]([O:12]C1C=CC=CC=1)=[O:11].[C:19]1([CH3:25])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>[OH-].[Na+]>[C:10]([N:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4])([O:12][CH2:25][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:11]

Participants

5

Reactant 3

HCID 1140TolueneHCID 15891Phenyl chloroformateHCID 145742L-Proline

Product 1

HCID 101987Benzyloxycarbonyl-L-prolineYield 98%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent2×

Conditions

Temperature
0 °C

Procedure

L-Proline (10 g, 86.6 mmol) was dissolved in 66 mL of 2N NaOH and cooled to 0° C. To this solution were slowly and simultaneously added 34.35 mL of a solution of phenyl chloroformate in toluene (104.2 mmol) and 33 mL of 4N NaOH, over a period of 1 hr, while maintaining the reaction temperature at 0° C. and the pH above 7. After all reactants were added, the reaction was stirred for 6 hr at room temperature. The solution was then extracted with ether. The remaining aqueous layer was neutralized to pH 6-7 with 1N HCl, then extracted with ethyl acetate. The extract was dried over Na2SO4 and concentrated to afford 21.19 g of the title product (98% yield). 1H NMR (CDCl3) δ 9.55 (d, 1H), 7.3 (s, 5H), 5.25 (d, 2H), 4.35 (t, 1H), 4.20 (t, 1H), 1.8-2.2 (m, 4H).

Workup

  1. temperaturewhile maintaining the reaction temperature at 0° C.
  2. additionAfter all reactants were added
  3. extractionThe solution was then extracted with ether
  4. extractionextracted with ethyl acetate
  5. dry with materialThe extract was dried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-c176d87d6c3c4a96ab95c902ab9d98fb
Source dataset
uspto-grants-1995_06
Patent number
US05424444

Linked notes

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