HCID 688299, compound → HCID 86696675, compound

HRID 1774178Notes

Reaction equation

HRID 1774178 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][C:3]=1[F:10].CON(C)[C:14]([C@H:16]1[CH2:20][CH2:19][CH2:18][N:17]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:15]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:14]([C@H:16]2[CH2:20][CH2:19][CH2:18][N:17]2[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:15])=[CH:4][C:3]=1[F:10]

Participants

4

Reactant 2

HCID 688299HCID 688299, compoundHCID 178505943HCID 178505943, compound

Product 1

HCID 86696675HCID 86696675, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

0.5M (4-Chloro-3-fluorophenyl)magnesium bromide (22.5 mL, 11.2 mmol) as a solution in THF was added dropwise to a cold (0° C.) solution of (R)-tert-butyl 2-(methoxy(methyl)carbamoyl)pyrrolidine-1-carboxylate (1.45 g, 5.61 mmol) in THF (25 mL) under N2, and the reaction was allowed to warm up to room temperature overnight. The next morning, the mixture was placed in an ice bath and carefully quenched with ice. The reaction mixture was concentrated. The residue was treated for 1 hour with a solution of 30% sodium potassium and then extracted with ethyl acetate (2×). The organic layer was dried, filtered and concentrated. The crude product was purified via column chromatography, eluting with hexanes/ethyl acetate (5:1) to give (R)-tert-butyl 2-(4-chloro-3-fluorobenzoyl)pyrrolidine-1-carboxylate (1.12 g, 61%). m/z (APCI-pos) (M+1)-Boc=228.1, 230.1.

Workup

  1. customThe next morning, the mixture was placed in an ice bath
  2. customcarefully quenched with ice
  3. concentrationThe reaction mixture was concentrated
  4. additionThe residue was treated for 1 hour with a solution of 30% sodium potassium
  5. extractionextracted with ethyl acetate (2×)
  6. customThe organic layer was dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified via column chromatography
  10. washeluting with hexanes/ethyl acetate (5:1)

Sources & evidence

ORD record
ord-f4bc7d0f868b4be3a58b39e60639b003
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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