Dimethylformamide → (R)-2-(3-formyl-benzyl)-morpholine-4-carboxylic acid tert-butyl ester

HRID 2253043Notes

Reaction equation

HRID 2253043 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])(C)(C)C.CN(C)[CH:29]=[O:30].[Cl-].[NH4+]>C(OCC)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH:29]=[O:30])[CH:16]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 67073309N-Boc-(R)-2-(3-bromobenzyl)morpholineHCID 178418306HCID 178418306, compound

Product 1

HCID 86607062(R)-2-(3-formyl-benzyl)-morpholine-4-carboxylic acid tert-butyl esterYield 43%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

The solution of 1.3 g (3.6 mmol) (R)-2-(3-bromo-benzyl)-morpholine-4-carboxylic acid tert-butyl ester in 80 mL diethyl ether was cooled down to −100° C. and treated dropwise with 2.6 mL (3.9 mmol; 1.5M solution in n-pentane) tert-butyllithium. After 15 min. 0.31 mL (4.0 mmol) N,N-dimethylformamide were added and the reaction stirred for another 1.5 h. The solution was poured on 10% aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel with n-hexane:ethyl acetate (2:1 v/v) as eluant to give the desired compound as colorless oil (43%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was chromatographed on silica gel with n-hexane:ethyl acetate (2:1 v/v) as eluant

Sources & evidence

ORD record
ord-331b8b1e0314441988ee17a142a05b03
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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