Water → Ethyl 3-{3-[(1S)-1,2-dihydroxyethyl]-4,5-difluorophenyl}propanoate

HRID 602035Notes

Reaction equation

HRID 602035 reaction equation
CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:22]C)C=C4)N(CC2)C1.[CH:59]([C:61]1[CH:62]=[C:63]([CH2:69][CH2:70][C:71]([O:73][CH2:74][CH3:75])=[O:72])[CH:64]=[C:65]([F:68])[C:66]=1[F:67])=[CH2:60].S([O-])([O-])=O.[Na+].[Na+].[OH2:82]>CC(O)(C)C>[OH:82][C@@H:59]([C:61]1[CH:62]=[C:63]([CH2:69][CH2:70][C:71]([O:73][CH2:74][CH3:75])=[O:72])[CH:64]=[C:65]([F:68])[C:66]=1[F:67])[CH2:60][OH:22]

Participants

6

Reactant 4

HCID 962Water3×HCID 24437Sodium SulfiteHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazineHCID 57470571Ethyl 3-(3-ethenyl-4,5-difluorophenyl)propanoate

Product 1

HCID 57470573Ethyl 3-{3-[(1S)-1,2-dihydroxyethyl]-4,5-difluorophenyl}propanoateYield 95%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of AD-mix-α (66.0 g), t-BuOH (340 mL), and H2O (380 mL) was stirred until no solid was observed and then cooled to 0° C. Ethyl 3-(3-ethenyl-4,5-difluorophenyl)propanoate (16.3 g, 68.0 mmol) in t-BuOH (45 mL) and H2O (5 mL) was added and the reaction stirred at 0° C. for 6 h and then warmed to room temperature overnight. Sodium sulfite (84 g) was added and the reaction stirred at room temperature for 5 h. The reaction was diluted with H2O and extracted two times with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered, and concentrated. Column chromatography (2-90% ethyl acetate:hexane) afforded the desired product (17.76 g, 95%).

Workup

  1. temperaturewarmed to room temperature overnight
  2. stirringthe reaction stirred at room temperature for 5 h
  3. extractionextracted two times with CH2Cl2
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-bab19201585747968f168cee0b343232
Source dataset
uspto-grants-2011_03
Patent number
US07902394B2

Reaction notes

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