3,4-dihydro-2H-pyran → (1R,3S,5S)-5-(Tetrahydro-pyran-2-yloxymethyl)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester 3-ethyl ester

HRID 1527430Notes

Reaction equation

HRID 1527430 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:11][C@:10]2([CH2:12][OH:13])[C@@H:8]([CH2:9]2)[N:7]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:5])[CH3:2].[O:21]1[CH:26]=[CH:25][CH2:24][CH2:23][CH2:22]1.CC1C=CC(S(O)(=O)=O)=CC=1.O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:11][C@:10]2([CH2:12][O:13][CH:22]3[CH2:23][CH2:24][CH2:25][CH2:26][O:21]3)[C@@H:8]([CH2:9]2)[N:7]1[C:14]([O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:15])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 682839112-(tert-Butyl) 3-ethyl (1R,3S,5S)-5-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate

Product 1

HCID 68284099(1R,3S,5S)-5-(Tetrahydro-pyran-2-yloxymethyl)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester 3-ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (1R,3S,5S)-5-hydroxymethyl-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylicacid 2-tert-butyl ester 3-ethyl ester (500 mg, 1.75 mmol), 3,4-dihydro-2H-pyran (176 μL, 1.93 mmol) and TsOH.H2O (33 mg, 0.17 mmol) in CH2Cl2 (6 mL) was stirred 3 h at RT. Then poured into a saturated aqueous solution of NaHCO3 and extracted with CH2Cl2 (×2). The combined organic extracts were 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). Colorless oil. TLC, Rf (EtOAc)=0.85; MS (UPLC/MS): 370.4 [M+H]+, 387.4 [M+H2O]+; tR (HPLC conditions f): 2.28 min.

Workup

  1. extractionextracted with CH2Cl2 (×2)
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 1:1)
  6. custom2.28 min.

Sources & evidence

ORD record
ord-9ba5124e67404540aee8f5800c8c3b84
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…