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

HRID 602045Notes

Reaction equation

HRID 602045 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]([CH:69]([CH2:76][CH3:77])[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+].[OH2:84]>CC(O)(C)C>[OH:84][C@@H:59]([C:61]1[CH:62]=[C:63]([CH:69]([CH2:76][CH3:77])[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 57470580Ethyl 3-(3-ethenyl-4,5-difluorophenyl)pentanoate

Product 1

HCID 57470582Ethyl 3-{3-[(1S)-1,2-dihydroxyethyl]-4,5-difluorophenyl}pentanoateYield 92%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of AD-mix-α (50.0 g), t-BuOH (250 mL), and H2O (280 mL) was stirred until no solid was observed and then cooled to 0° C. Ethyl 3-(3-ethenyl-4,5-difluorophenyl)pentanoate (12.58 g, 0.0469 mol) in t-BuOH (35 mL) and H2O (10 mL) was added and the reaction stirred at 0° C. for 6 h and then warmed to room temperature overnight. Sodium sulfite (64 g) was added to quench the reaction and the reaction was diluted with H2O and extracted three times with ethylacetate. The combined organic layers were dried over Na2SO4, filtered, and concentrated. Column chromatography (hexane:ethylacetate, 7:3) yielded the desired product (13.02 g, 92%).

Workup

  1. temperaturewarmed to room temperature overnight
  2. customto quench
  3. customthe reaction
  4. extractionextracted three times with ethylacetate
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-6ff6083404aa4bf8a6eed429426566e9
Source dataset
uspto-grants-2011_03
Patent number
US07902394B2

Reaction notes

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