Triethylamine → (S)-(-)-N-Boc-prolinol

HRID 974774Notes

Reaction equation

HRID 974774 reaction equation
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10](O)=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.ClC(OCC)=O>C1COCC1.[Cl-].[Na+].O>[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[CH2:10][OH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-

Product 1

HCID 643448(S)-(-)-N-Boc-prolinol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of BOC-(L)-proline in 60 ml of anhydrous THF, cooled at -10° C. with brine, is added with 6.1 ml of triethylamine and 1 g of 4 A molecular sieves, then, keeping the temperature below -5° C., a solution of 4.16 ml of ethyl chloroformate in 5 ml of anhydrous THF is dropped therein. After 30 minutes under stirring, the reaction mixture is filtered to remove the triethylammonium chloride precipitate and the filtrate is concentrated under reduced pressure to a volume of 30 ml. The resulting solution is dropped into a suspension of 7.5 g of sodium borohydride in 50 ml of anhydrous THF, cooled at -10° C. with brine. After 2 hours the reaction mixture is added with 200 ml of an aqueous saturated solution of sodium dihydrogen phosphate, keeping the temperature at 0° C. with water/ice, then it is extracted with ethyl acetate (3×50 ml). The combined organic extracts are washed repeatedly with an aqueous saturated solution of sodium bicarbonate (3×30 ml), dried over sodium sulfate and the solvent is evaporated off under reduced pressure. The residue, by crystallization from hexane, yields 6.1 g of BOC-(L)-prolinol, m.p. 59°-60° C., [α]D =-54.9° (c=0.2 in EtOH).

Workup

  1. customthe temperature below -5° C.
  2. filtrationthe reaction mixture is filtered
  3. customto remove the triethylammonium chloride precipitate
  4. concentrationthe filtrate is concentrated under reduced pressure to a volume of 30 ml
  5. additionThe resulting solution is dropped into a suspension of 7.5 g of sodium borohydride in 50 ml of anhydrous THF
  6. additionAfter 2 hours the reaction mixture is added with 200 ml of an aqueous saturated solution of sodium dihydrogen phosphate
  7. customat 0° C.
  8. extractionit is extracted with ethyl acetate (3×50 ml)
  9. washThe combined organic extracts are washed repeatedly with an aqueous saturated solution of sodium bicarbonate (3×30 ml)
  10. dry with materialdried over sodium sulfate
  11. customthe solvent is evaporated off under reduced pressure
  12. customThe residue, by crystallization from hexane

Sources & evidence

ORD record
ord-434363e9d2c340ba908d3d7a01ccf5b3
Source dataset
uspto-grants-1997_03
Patent number
US05607930

Reaction notes

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