Water → HCID 58885772, compound

HRID 425953Notes

Reaction equation

HRID 425953 reaction equation
C[C:2]([OH:5])([CH3:4])[CH3:3].[Cl:6][C:7]1[C:12]([F:13])=[CH:11][CH:10]=[C:9]([Cl:14])[C:8]=1[CH:15]([O:17][C:18]1[C:19]([NH2:26])=[N:20][CH:21]=C(C=C)[CH:23]=1)[CH3:16].[OH2:27]>>[NH2:26][C:19]1[N:20]=[CH:21][C:3]([C@H:2]([OH:5])[CH2:4][OH:27])=[CH:23][C:18]=1[O:17][CH:15]([C:8]1[C:9]([Cl:14])=[CH:10][CH:11]=[C:12]([F:13])[C:7]=1[Cl:6])[CH3:16]

Participants

4

Reactant 3

HCID 962Water2×HCID 6386tert-ButanolHCID 21110804HCID 21110804, compound

Product 1

HCID 58885772HCID 58885772, compoundYield 53%

Conditions

Temperature
0 °C

Procedure

(S)-1-{6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-ethane-1,2-diol was prepared as follow: To a solution of asymmetic dihydroxylation-mix α (2.33 g) in a 1:1 mixture of t-BuOH and water (8 mL each) cooled to 0° C. was added 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-vinyl-pyridin-2-ylamine (500 mg, 1.67 mmol). The reaction mixture was stirred at 0° C. until consumption of the starting material. Three more loadings of AD-mix α was added periodically to increase the reaction rate. Water was added (5 mL) and the mixture was extracted with EtOAc (3×20 mL). The combined organic layer was dried over Na2SO4, and concentrated. The crude product was purified by reverse phase HPLC to provide (S)-1-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}ethane-1,2-diol (320 mg, 53% yield).

Workup

  1. custom(S)-1-{6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-ethane-1,2-diol was prepared
  2. additionTo a solution of asymmetic dihydroxylation-mix α (2.33 g)
  3. additionThree more loadings of AD-mix α was added periodically
  4. temperatureto increase the reaction rate
  5. extractionthe mixture was extracted with EtOAc (3×20 mL)
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-26da4ac61d03469dbe46b53d4bfd6561
Source dataset
uspto-grants-2012_01
Patent number
US08106197B2

Reaction notes

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