Formic Acid → (R)-4-((S)-1-hydroxyethyl)-1-((S)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 715726Notes

Reaction equation

HRID 715726 reaction equation
C1(C)C=CC(S(N[C@H](C2C=CC=CC=2)[C@@H](C2C=CC=CC=2)N)(=O)=O)=CC=1.[C:27]([C@H:30]1[CH2:34][N:33]([C@H:35]([C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=2)[CH3:36])[C:32](=[O:45])[CH2:31]1)(=[O:29])[CH3:28].C(O)=O.Cl>C(#N)C.C[C]1[C](C)[C](C)[C](C)[C]1C.C[C]1[C](C)[C](C)[C](C)[C]1C.Cl[Rh]Cl.Cl[Rh]Cl.C(N(CC)CC)C>[OH:29][C@H:27]([C@H:30]1[CH2:34][N:33]([C@H:35]([C:37]2[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=2)[CH3:36])[C:32](=[O:45])[CH2:31]1)[CH3:28]

Participants

8

Reactant 4

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 2734565N-((1R,2R)-2-Amino-1,2-diphenylethyl)-4-methylbenzene-1-sulfonamideHCID 58071853(R)-4-Acetyl-1-((S)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Product 1

HCID 58071870(R)-4-((S)-1-hydroxyethyl)-1-((S)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-oneYield 113.3%

Reagents, catalysts & solvents 3

HCID 16212157Bis[(pentamethylcyclopentadienyl)dichloro-rhodium]CatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-15 °C

Procedure

2.4 g of Dichloro-(pentamethylcyclopentadienyl)-rhodium-(III)-dimer and 2.8 g (R,R)—N-(p-toluenesulfonyl)-1,2-diphenylethylendiamine [(R,R)-TsDPEN] is added to a solution of 50 g (R)-4-acetyl-1-[(S)-1-(4-methoxyphenyl)-ethyl]pyrrolidine-2-one in acetonitril at 25° C. The solution is cooled to −15° C. At this temperature a mixture of 22 mL formic acid and 135 mL triethylamine is added. The reaction mixture is stirred for 22 hours at −15° C. and then warmed up to 20° C. 230 mL of a 4 molar hydrochloric acid is added under cooling. The aqueous phase is extracted 3 times with ethyl acetate. The organic phase is washed with diluted and concentrated brine and treated with activated carbon. The organic phase is dried over sodium sulfate. The solvent is evaporated under reduced pressure to obtain 57.1 g of a beige solid with a diastereomeric purity of ˜97:3.

Workup

  1. additionis added
  2. temperaturewarmed up to 20° C
  3. temperatureunder cooling
  4. extractionThe aqueous phase is extracted 3 times with ethyl acetate
  5. washThe organic phase is washed
  6. additionwith diluted
  7. additionconcentrated brine and treated with activated carbon
  8. dry with materialThe organic phase is dried over sodium sulfate
  9. customThe solvent is evaporated under reduced pressure

Sources & evidence

ORD record
ord-61b506fda00a4973bd9ed0302550fb6f
Source dataset
uspto-grants-2015_11
Patent number
US09187478B2

Reaction notes

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