Potassium Carbonate → 2(R)-(4-methoxy-2,3,6-trimethylbenzenesulfonylamino)-3(S)-hydroxy-butyric acid 3,4-methylenedioxybenzyl ester

HRID 1006131Notes

Reaction equation

HRID 1006131 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([NH:13][C@H:14]([C@@H:18]([OH:20])[CH3:19])[C:15]([OH:17])=[O:16])(=[O:12])=[O:11])=[C:5]([CH3:21])[C:4]=1[CH3:22].C(=O)([O-])[O-].[K+].[K+].[CH2:29]1[O:39][C:38]2[CH:37]=[CH:36][C:33]([CH2:34]Cl)=[CH:32][C:31]=2[O:30]1.[I-].[Li+]>CN(C)C=O.C(Cl)Cl>[CH2:29]1[O:39][C:38]2[CH:37]=[CH:36][C:33]([CH2:34][O:16][C:15](=[O:17])[C@H:14]([NH:13][S:10]([C:6]3[C:7]([CH3:9])=[CH:8][C:3]([O:2][CH3:1])=[C:4]([CH3:22])[C:5]=3[CH3:21])(=[O:11])=[O:12])[C@@H:18]([OH:20])[CH3:19])=[CH:32][C:31]=2[O:30]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 887131,3-Benzodioxole, 5-(chloromethyl)-HCID 183375572(R)-(4-methoxy-2,3,6-trimethylbenzenesulfonylamino)-3(S)-hydroxybutyric acid

Product 1

HCID 865900252(R)-(4-methoxy-2,3,6-trimethylbenzenesulfonylamino)-3(S)-hydroxy-butyric acid 3,4-methylenedioxybenzyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2(R)-(4-methoxy-2,3,6-trimethylbenzenesulfonylamino)-3(S)-hydroxybutyric acid (29.13 g, 87.9 mmol) in dimethylformamide (280 mL) at 0° C., was added potassium carbonate (72.9 g, 527 mmol) and a solution of 3,4-methylenedioxybenzyl chloride ((60 g, 170.8 mmol, 50% (w/w)) in methylene chloride. After 2 h, lithium iodide (5.88 g, 44 mmol) was added and the reaction mixture was warmed to rt. over 2 h. After 6 h, the reaction mixture was partitioned between ethyl acetate (600 mL) and water (250 mL). The organic layer was separated, dried over magnesium sulfate and concentrated in vacuo. The crude residue was chromatographed (300 g SiO2, 15% ethyl acetate-hexanes) to afford 2(R)-(4-methoxy-2,3,6-trimethylbenzenesulfonylamino)-3(S)-hydroxy-butyric acid 3,4-methylenedioxybenzyl ester (40.4 g), a portion which was taken directly into the next reaction without further purification.

Workup

  1. waitover 2 h
  2. waitAfter 6 h
  3. customthe reaction mixture was partitioned between ethyl acetate (600 mL) and water (250 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was chromatographed (300 g SiO2, 15% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-932bffced4ed4455b1191deff824f7fd
Source dataset
uspto-grants-2004_09
Patent number
US06787559B2

Reaction notes

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