Ethyl Acetate → (S)-N-((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-hydroxyethyl)-2-methylpropane-2-sulfinamide

HRID 455691Notes

Reaction equation

HRID 455691 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:35][CH2:36][O:37][CH3:38])=[C:6]([C@@:8]([C:21]2[CH:26]=[C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:24]=[C:23]([F:33])[C:22]=2[Cl:34])([NH:14][S@:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[O:16])[C:9](OCC)=[O:10])[CH:7]=1.CC(C[AlH]CC(C)C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+].CCOC(C)=O>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:35][CH2:36][O:37][CH3:38])=[C:6]([C@:8]([NH:14][S@:15]([C:17]([CH3:18])([CH3:19])[CH3:20])=[O:16])([C:21]2[CH:26]=[C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:24]=[C:23]([F:33])[C:22]=2[Cl:34])[CH2:9][OH:10])[CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 14487Diisobutylaluminum hydride3×HCID 9855836Potassium sodium tartarateHCID 86658387(S)-ethyl 2-(5-bromo-2-(methoxymethoxy)phenyl)-2-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-((S)-1,1-dimethylethylsulfinamido)acetate

Product 1

HCID 67440021(S)-N-((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-hydroxyethyl)-2-methylpropane-2-sulfinamideYield 57.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-ethyl 2-(5-bromo-2-(methoxymethoxy)phenyl)-2-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-((S)-1,1-dimethylethylsulfinamido)acetate (3.56 g, 5.59 mmol) in THF (60 mL) was cooled to 0° C. and treated drop wise with DIBAL (1M in THF) (22.36 mL, 22.36 mmol) under nitrogen atmosphere. After 1 h additional 10 mL DIBAL solution were added at RT. After 12 h at RT additional 10 mL DIBAL solution were added. After 30 min aqueous saturated solution of potassium sodium tartrate was added, followed by EtOAc. The reaction mixture was allowed to stir vigorously for 1 h. The organic phase was separated, washed with aqueous saturated solution of potassium sodium tartrate and dried over MgSO4. The solvent was removed under reduced pressure and the crude material was purified by silica gel chromatography (20-100% EtOAc/hexane) to provide 1.90 g of (S)—N—((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-hydroxyethyl)-2-methylpropane-2-sulfinamide.

Workup

  1. customThe organic phase was separated
  2. washwashed with aqueous saturated solution of potassium sodium tartrate
  3. dry with materialdried over MgSO4
  4. customThe solvent was removed under reduced pressure
  5. customthe crude material was purified by silica gel chromatography (20-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-9af7af164d6c4cc482ce20f08374690c
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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