Acetic Acid → (S)-ethyl 2-(5-bromo-2-(methoxymethoxy)phenyl)-2-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-((S)-1,1-dimethylethylsulfinamido)acetate

HRID 455690Notes

Reaction equation

HRID 455690 reaction equation
CC1(C)CCCC(C)(C)N1.[Li]CCCC.[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[N:21][C:22]=1[F:23].[Br:30][C:31]1[CH:32]=[CH:33][C:34]([O:50][CH2:51][O:52][CH3:53])=[C:35]([C:37](=[N:43][S@:44]([C:46]([CH3:49])([CH3:48])[CH3:47])=[O:45])[C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:36]=1.C(O)(=O)C>C1COCC1>[Br:30][C:31]1[CH:32]=[CH:33][C:34]([O:50][CH2:51][O:52][CH3:53])=[C:35]([C@@:37]([C:18]2[CH:19]=[C:20]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[N:21]=[C:22]([F:23])[C:17]=2[Cl:16])([NH:43][S@:44]([C:46]([CH3:49])([CH3:47])[CH3:48])=[O:45])[C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:36]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 130352,2,6,6-TetramethylpiperidineHCID 574756574-(5-Chloro-6-fluoropyridin-2-yl)morpholineHCID 86658358(S)-ethyl 2-(5-bromo-2-(methoxymethoxy)phenyl)-2-(tert-butylsulfinylimino)acetateHCID 178418339Butyllithium

Product 1

HCID 86658387(S)-ethyl 2-(5-bromo-2-(methoxymethoxy)phenyl)-2-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-((S)-1,1-dimethylethylsulfinamido)acetateYield 67.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 2,2,6,6-tetramethylpiperidine (1.897 mL, 11.24 mmol) in THF (45 mL) was cooled to −78° C. and treated with n-BuLi (1.6M in hexanes) (6.77 mL, 10.83 mmol) under nitrogen atmosphere. The solution was warmed to 0° C. and stirred at that temperature for 25 minutes. The solution was cooled back down to −78° C. and treated with a solution of 4-(5-chloro-6-fluoropyridin-2-yl)morpholine (2.165 g, 9.99 mmol) in THF (11.25 mL) under nitrogen atmosphere. The solution was allowed to stir at that temperature for 40 minutes and then added drop wise via cannula to a solution of (S)-ethyl 2-(5-bromo-2-(methoxymethoxy)phenyl)-2-(tert-butylsulfinylimino)acetate (3.5 g, 8.33 mmol) in THF (11.25 mL) also cooled to −78° C. under nitrogen atmosphere. The reaction mixture was allowed to stir at −78° C. for additional 2 hours and then quenched with acetic acid (0.715 mL, 12.49 mmol). The reaction mixture was allowed to warm to RT overnight. The solvent was removed under reduced pressure and the crude material was purified by silica gel chromatography (10-60% EtOAc/hexane) to afford 3.56 g (S)-ethyl 2-(5-bromo-2-(methoxymethoxy)phenyl)-2-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-((S)-1,1-dimethylethylsulfinamido)acetate.

Workup

  1. temperatureThe solution was cooled back down to −78° C.
  2. stirringto stir at that temperature for 40 minutes
  3. temperaturealso cooled to −78° C. under nitrogen atmosphere
  4. stirringto stir at −78° C. for additional 2 hours
  5. temperatureto warm to RT overnight
  6. customThe solvent was removed under reduced pressure
  7. customthe crude material was purified by silica gel chromatography (10-60% EtOAc/hexane)

Sources & evidence

ORD record
ord-460719fcfa554d31abdd39c135d85f53
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

Loading…