Methanamine, N-methoxy-, hydrochloride (1:1) → (3R,4S)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carboxylic acid methoxy-methyl-amide

HRID 906932Notes

Reaction equation

HRID 906932 reaction equation
Cl.CN[O:4][CH3:5].C[Al](C)C.C([C@H:17]1COC(=O)[N:18]1[C:23]([C@@H:25]1[C@@H:29]([C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=2)[CH2:28][N:27]([CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:26]1)=[O:24])C1C=CC=CC=1>C(Cl)Cl>[CH3:5][O:4][N:18]([CH3:17])[C:23]([C@@H:25]1[C@@H:29]([C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=2)[CH2:28][N:27]([CH2:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH2:26]1)=[O:24]

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 16682925TrimethylaluminumHCID 67131796(S)-4-benzyl-3-[(3R,4S)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carbonyl]-oxazolidin-2-one

Product 1

HCID 86627622(3R,4S)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carboxylic acid methoxy-methyl-amideYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of N,O-dimethylhydroxylamine hydrochloride (3.61 g, 0.037 mol) in DCM (40 mL) at RT was added trimethylaluminium (2.0M solution in heptane, 18.5 ml, 0.037 mol) dropwise and stirring was continued for one hour. To this mixture was added a solution of (S)-4-benzyl-3-[(3R,4S)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carbonyl]-oxazolidin-2-one (9.47 g, 0.0186 mol) in DCM (50 mL) over 10 minutes. Stirring was continued for three hours. The reaction was quenched by an addition of aq. Potassium sodium tartarate solution and extracted with ethyl acetate. The separated organic layer was washed with brine and dried on Na2SO4 and concentrated under vacuo. Purification by column chromatography (SiO2, EtOAc/H, 2:3) yielded 6.58 g (90%) of the title compound as a light yellow oil. ES-MS m/e: 393.1 (M+H+).

Workup

  1. stirringStirring
  2. waitwas continued for three hours
  3. customThe reaction was quenched by an addition of aq. Potassium sodium tartarate solution
  4. extractionextracted with ethyl acetate
  5. washThe separated organic layer was washed with brine
  6. customdried on Na2SO4
  7. concentrationconcentrated under vacuo
  8. customPurification by column chromatography (SiO2, EtOAc/H, 2:3)

Sources & evidence

ORD record
ord-fefbfaf3de73440f911f86c248f372b8
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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