Lithium borohydride → (S)-1-(1-(3-chloro-5-(hydroxymethyl)pyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

HRID 408011Notes

Reaction equation

HRID 408011 reaction equation
[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:22][CH2:21][C@H:20]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][C:25]=4[F:34])[C:19]3=[O:35])[CH2:14][CH2:13]2)=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7](OC)=[O:8].[Li+].[BH4-]>C1COCC1.C(Cl)Cl>[Cl:1][C:2]1[C:3]([N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[CH2:22][CH2:21][C@H:20]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:26][C:25]=4[F:34])[C:19]3=[O:35])[CH2:16][CH2:17]2)=[N:4][CH:5]=[C:6]([CH2:7][OH:8])[CH:11]=1

Participants

5

Reactant 2

HCID 4148881Lithium borohydrideHCID 67469943(S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinate

Product 1

HCID 54670713(S)-1-(1-(3-chloro-5-(hydroxymethyl)pyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-oneYield 11.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinate (0.20 g, 0.38 mmol) in THF (20 mL) was added LiBH4 (2 M in THF, 0.19 mL, 0.38 mmol) and the reaction was stirred overnight at ambient temperature. The reaction was diluted with DCM (50 mL) and the organic layer was washed with water (20 mL), 1 N HCl (10 mL), 1 N NaOH (10 mL) and brine (10 mL), and the combined organic phases were dried over MgSO4, filtered and concentrated under vacuum. The crude material was purified on silica using EtOAc as eluent to yield a solid, which was further triturated with isopropanol/hexanes to give (S)-1-(1-(3-chloro-5-(hydroxymethyl)pyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (0.021 g, 0.043 mmol, 11% yield). Mass spectrum (apci) m/z=497.0 (M+H+).

Workup

  1. washthe organic layer was washed with water (20 mL), 1 N HCl (10 mL), 1 N NaOH (10 mL) and brine (10 mL)
  2. dry with materialthe combined organic phases were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe crude material was purified on silica
  6. customto yield a solid, which
  7. customwas further triturated with isopropanol/hexanes

Sources & evidence

ORD record
ord-d0f5f545afb04462b3143d31d7fa238b
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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