tert-butyl(2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanoate → 1-[(1S)-1-(tertbutoxycarbonyl)propyl]-5-oxo-3-pyrrolidinecaboxaldehyde

HRID 1072575Notes

Reaction equation

HRID 1072575 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:7][N:6]([C@@H:8]([CH2:16][CH3:17])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:5](=[O:18])[CH2:4]1>C(Cl)Cl.N1C=CC=CC=1>[C:12]([O:11][C:9]([C@@H:8]([N:6]1[C:5](=[O:18])[CH2:4][CH:3]([CH:2]=[O:1])[CH2:7]1)[CH2:16][CH3:17])=[O:10])([CH3:15])([CH3:13])[CH3:14]

Participants

4

Reactant 1

HCID 57478730tert-butyl(2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanoate

Product 1

HCID 183461161-[(1S)-1-(tertbutoxycarbonyl)propyl]-5-oxo-3-pyrrolidinecaboxaldehydeYield 49.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

In a three necked flask, under argon, a solution of tert-butyl(2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanoate 398 (4.0 g, 0.016 mol.) in CH2Cl2 (8 ml) is added to a suspension of CrO3 (6.2 g, 0.062 mol.) in pyridine (111.3 ml)/CH2Cl2 (80 ml) stirred at room temperature. The temperature increases to 30° C. and the suspension is stirred for 0.2 h. The suspension is filtered through celite and the filtrate is washed successively with HCl 1N, brine, dried over magnesium sulfate and concentrated in vacuo to afford the crude aldehyde which is purified by column chromatography on silicagel (hexane/acetone 70/30 (v/v)) to afford 2.03 g of 1-[(1S)-1-(tertbutoxycarbonyl)propyl]-5-oxo-3-pyrrolidinecarboxaldehyde 396 (41%). Alternatively, the reaction can also be conducted with racemic ester to afford the racemic aldehyde with a similar yield. Analysis of a 1/1 mixture of 1-[(1S)-1-(tertbutoxycarbonyl)propyl]-5-oxo-3-pyrrolidinecarboxaldehyde 396: 1H NMR (250 MHz, (CDCl3): 0.91 (t, 3H), 1.44 (s, 9H), 1.55-1.77 (m, 1H), 1.90-2.15 (m, 1H), 2.63-2.82 (m, 2H), 3.47-3.61 (m, 1H), 3.65-3.79 (m, 1H), 3.83-3.94 (m, 1H of one of the diastereoisomers), 4.48-4.62 (m, 1H), 9.74 (s (broad), 1H).

Workup

  1. temperatureThe temperature increases to 30° C.
  2. stirringthe suspension is stirred for 0.2 h
  3. filtrationThe suspension is filtered through celite
  4. washthe filtrate is washed successively with HCl 1N, brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto afford the crude aldehyde which
  8. customis purified by column chromatography on silicagel (hexane/acetone 70/30 (v/v))

Sources & evidence

ORD record
ord-a23b28eecce94171a82366f2dd6e8529
Source dataset
uspto-grants-2005_06
Patent number
US06911461B2

Reaction notes

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