Acetic Acid → (3R*,4S*)-3-[2-(tert-Butoxy)-2-oxoethyl]-1-[(2,6-dichlorophenyl)methyl]-4-methylpyrrolidine-3-carboxylic acid

HRID 446005Notes

Reaction equation

HRID 446005 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:25]([O:29][C:30](=[O:41])[CH2:31][C@@:32]1([C:38]([OH:40])=[O:39])[C@H:36]([CH3:37])[CH2:35][NH:34][CH2:33]1)([CH3:28])([CH3:27])[CH3:26].C(O)(=O)C>O.CO>[C:25]([O:29][C:30](=[O:41])[CH2:31][C@@:32]1([C:38]([OH:40])=[O:39])[C@H:36]([CH3:37])[CH2:35][N:34]([CH2:4][C:3]2[C:2]([Cl:1])=[CH:9][CH:8]=[CH:7][C:6]=2[Cl:10])[CH2:33]1)([CH3:26])([CH3:27])[CH3:28]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 67372,6-Dichlorobenzaldehyde2×HCID 5049666Sodium triacetoxyborohydride2×HCID 71293641(3R,4S)-3-[2-(tert-butoxy)-2-oxoethyl]-4-methylpyrrolidine-3-carboxylic acid

Product 1

HCID 71293674(3R*,4S*)-3-[2-(tert-Butoxy)-2-oxoethyl]-1-[(2,6-dichlorophenyl)methyl]-4-methylpyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

2,6-Dichlorobenzaldehyde (646 mg, 3.7 mmol) and sodium triacetoxyborohydride (782 mg, 3.7 mmol) were added to a mixture of (3R*,4S*)-3-[2-(tert-butoxy)-2-oxoethyl]-4-methylpyrrolidine-3-carboxylic acid obtained by the method of Example 2j (600 mg, 2.47 mmol), acetic acid (0.14 ml, 2.47 mmol) and methanol (10 ml), and the reaction mixture was stirred at room temperature for two hours. 2,6-Dichlorobenzaldehyde (430 mg, 2.5 mmol) and sodium triacetoxyborohydride (522 mg, 2.5 mmol) were further added, followed by stirring at an external temperature of 40° C. for 10.5 hours. Water was added to the reaction mixture, which was extracted with dichloromethane five times, and the organic layer was concentrated. The residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/methanol) to give Lot A (32 mg) and Lot B (551 mg) of the title compound.

Workup

  1. stirringby stirring at an external temperature of 40° C. for 10.5 hours
  2. extractionwas extracted with dichloromethane five times
  3. concentrationthe organic layer was concentrated
  4. customThe residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/methanol)

Sources & evidence

ORD record
ord-15762589c0ed489db2df78c29c1a6b58
Source dataset
uspto-grants-2013_07
Patent number
US08476301B2

Reaction notes

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