Dimethylformamide → O1-tert-butyl O2-ethyl (2S)-4-formyl-2,3-dihydropyrrole-1,2-dicarboxylate

HRID 1527420Notes

Reaction equation

HRID 1527420 reaction equation
O=P(Cl)(Cl)Cl.CN([CH:9]=[O:10])C.[CH3:11][CH2:12][O:13][C:14]([C@@H:16]1[CH2:20][CH:19]=[CH:18][N:17]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:15].[OH-].[Na+]>C(Cl)Cl>[CH3:11][CH2:12][O:13][C:14]([C@@H:16]1[CH2:20][C:19]([CH:9]=[O:10])=[CH:18][N:17]1[C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])=[O:15]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 10562087Ethyl N-boc-L-proline-4-ene

Product 1

HCID 86673854O1-tert-butyl O2-ethyl (2S)-4-formyl-2,3-dihydropyrrole-1,2-dicarboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

POCl3 (7.59 mL, 83 mmol) was added in 25 min at 0° C. under N2 atmosphere to DMF (6.39 mL, 83 mmol) and the mixture was stirred at RT for 20 min. Dry CH2Cl2 (150 mL) was added at 0° C., followed by a solution of (S)-2,3-dihydro-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (10 g, 41.4 mmol) in CH2Cl2 (50 mL). The mixture was stirred 30 min at RT until completion. The mixture was slowly poured into an ice cold aqueous solution of NaOH 10 N (150 mL) and extracted with CH2Cl2 (×3). The combined organic extracts were washed with brine (×2), with water, dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 9:1) to give the desired material as a yellow oil. Rf, TLC (c-hexane/EtOAc 4:1)=0.2; MS (UPLC-MS): 270 [M+H]+, 170 [M−Boc]−; tR (HPLC conditions f): 1.93 min.

Workup

  1. stirringThe mixture was stirred 30 min at RT until completion
  2. extractionextracted with CH2Cl2 (×3)
  3. washThe combined organic extracts were washed with brine (×2), with water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 9:1)

Sources & evidence

ORD record
ord-01a1db0192734cf387e5ff95e2ef1a8f
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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