Dichloromethane → (+/-)-(4R*,5R*)-5-{(1 S *)[5-(3-chloro-4-fluorophenyl) (2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one

HRID 1837992Notes

Reaction equation

HRID 1837992 reaction equation
Br[C:2]1[S:6][C:5]([C@@H:7]([OH:21])[C@@H:8]2[N:12]([CH3:13])[C:11](=[O:14])[CH2:10][C@@H:9]2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.[Cl:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][C:28]=1[F:29].C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:22][C:23]1[CH:24]=[C:25]([C:2]2[S:6][C:5]([C@@H:7]([OH:21])[C@@H:8]3[N:12]([CH3:13])[C:11](=[O:14])[CH2:10][C@@H:9]3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:4][CH:3]=2)[CH:26]=[CH:27][C:28]=1[F:29]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 69891005(4R*,5R*)-5-[(1S*)(5-bromo(2-thienyl))hydroxymethyl]-1-methyl-4-phenylpyrrolidin-2-one

Product 1

HCID 86587929(+/-)-(4R*,5R*)-5-{(1 S *)[5-(3-chloro-4-fluorophenyl) (2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-oneYield 69%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of (±)-(4R*,5R*)-5-[(1S*)(5-bromo(2-thienyl))hydroxymethyl]-1-methyl-4-phenylpyrrolidin-2-one (300 mg, 0.82 mmol) in 1,2-dimethoxyethane (2.8 mL) was added 3-chloro-4-fluorobenzeneboronic acid (85.9 mg, 1.07 mmol), followed by a 1M Na2CO3 solution (2.2 mL). A catalytic amount of Pd(PPh3)4 was added and the reaction mixture was heated at the reflux temperature for 3 h, then allowed to cool to room temperature and poured onto a mixture of ice and CH2Cl2. The resulting mixture was extracted with CH2Cl2, dried (MgSO4) and concentrated under reduced pressure. The crude product was triturated (Et2O/ cyclohexane) to give (±)-(4R*,5R*)-5-{(1S*)[5-(3-chloro-4-fluorophenyl)(2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one (235 mg, 69%): mp 194° C.; TLC (EtOAc) Rf 0.47

Workup

  1. temperaturethe reaction mixture was heated at the reflux temperature for 3 h
  2. extractionThe resulting mixture was extracted with CH2Cl2
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was triturated (Et2O/ cyclohexane)

Sources & evidence

ORD record
ord-c13caf419e944782b8a7a6eefc08298e
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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