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

HRID 1527421Notes

Reaction equation

[CH3:1][CH2:2][O:3][C:4]([C@@H:6]1[CH2:10][C:9]([CH:11]=[O:12])=[CH:8][N:7]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:5].[BH4-].[Na+].CO>C(Cl)Cl>[CH3:1][CH2:2][O:3][C:4]([C@@H:6]1[CH2:10][C:9]([CH2:11][OH:12])=[CH:8][N:7]1[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])=[O:5]

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of (S)-4-formyl-2,3-dihydro-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (3.32 g, 12.3 mmol) in CH2Cl2 (51.4 mL) was cooled at −78° C. under nitrogen atmosphere, solid NaBH4 (1 g, 24.7 mmol) was added portionwise maintaining the temperature at −78° C. MeOH (25.7 mL) was added dropwise and the reaction mixture was allowed to reach 0° C. and was stirred 1 h30 at 0° C. The reaction was quenched with an aqueous saturated solution of NH4Cl and extracted with CH2Cl2 (×3). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 1:1 to EtOAc) to give the desired material as a yellow oil. Rf, TLC (c-hexane/EtOAc 1:1)=0.30; MS (UPLC-MS): 272.2 [M+H]+, 316 [M+HCOO]−; tR (HPLC conditions f): 1.74 min.

Workup

customto reach 0° C.
customThe reaction was quenched with an aqueous saturated solution of NH4Cl
extractionextracted with CH2Cl2 (×3)
washThe combined organic layers were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 1:1 to EtOAc)

Sources & evidence

ORD record: ord-ed355c0261ab497b96f001aa982334fe
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085555B2

Reaction notes

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