2,4-Difluorophenylboronic acid → HCID 53474283, compound

HRID 2037547Notes

Reaction equation

HRID 2037547 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([N:10]2[CH2:15][CH2:14][C@@:13]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)([CH2:16][CH2:17][OH:18])[O:12][C:11]2=[O:26])[CH3:9])=[CH:4][CH:3]=1.[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1B(O)O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([N:10]2[CH2:15][CH2:14][C@@:13]([C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)([CH2:16][CH2:17][OH:18])[O:12][C:11]2=[O:26])[CH3:9])=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 27343342,4-Difluorophenylboronic acidHCID 59532381HCID 59532381, compound

Product 1

HCID 53474283HCID 53474283, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-3-((R)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one (109 mg, 0.26 mmol), 2,4-difluorophenylboronic acid (49 mg, 0.31 mmol) and Pd(PPh3)4 (30 mg, 0.03 mmol) in dioxane (8 mL) was added a solution of CsCO3 (2 M, 1 mL) at 0□. Then the reaction mixture was refluxed overnight under nitrogen. The reaction mixture was washed with water and then extract with CH2Cl2 twice. The combined organic phases were dried over Na2SO4, filtered and concentrated to give the residue, which was purified by preparative HPLC to afford (S)-3-((R)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one (49 mg, 42%). LC-MS Method 3 tR=1.41, min, m/z=456; 1H NMR (CD3OD): 1.55 (m, 3H), 2.12 (m, 2H), 2.22-2.46 (m, 3H), 2.52 (m, 1H), 3.12 (m, 1H), 3.33 (m, 1H), 3.68 (m, 1H), 5.56 (m, 1H), 7.08 (m, 6H), 7.08 (m, 2H), 7.35 (m, 5H). 443-155-3.

Workup

  1. temperatureThen the reaction mixture was refluxed overnight under nitrogen
  2. washThe reaction mixture was washed with water
  3. extractionextract with CH2Cl2 twice
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the residue, which
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-50cc55c678b44f158fd137f21f022348
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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