Cesium carbonate → Benzyl 2-(3-fluoro-4-((2-methoxyethoxy)methyl)phenyl)acrylate

HRID 1842922Notes

Reaction equation

HRID 1842922 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][CH2:10][CH2:11][O:12][CH3:13].C([O-])([O-])=O.[Cs+].[Cs+].Br[C:30](=[CH2:41])[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32]>CN(C=O)C.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:3]=[C:4]([C:30](=[CH2:41])[C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:32])[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][CH2:10][CH2:11][O:12][CH3:13]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 13443472Benzyl 2-bromoprop-2-enoateHCID 596373292-{3-Fluoro-4-[(2-methoxyethoxy)methyl]phenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolane2×

Product 1

HCID 59637287Benzyl 2-(3-fluoro-4-((2-methoxyethoxy)methyl)phenyl)acrylateYield 25.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 2-(3-fluoro-4-((2-methoxyethoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5 g, 16.129 mmol), Cs2CO3 (15.7 g, 48.38 mmol) in DMF (50 mL) was deoxygenated by purging Argon for 30 min at RT. Pd(dppf)Cl2 (657 mg, 0.806 mmol) was added and purging was continued. After 10 min, benzyl 2-bromoacrylate (4.6 g, 19.35 mmol) was added and stirred at 100° C. for 1 h until complete consumption of 2-(3-fluoro-4-((2-methoxyethoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, as evidenced by TLC analysis. The reaction mixture was diluted with ethyl acetate (200 mL), filtered through a celite pad, washed with ethyl acetate (2×25 mL). The filtrate was washed with water (2×100 mL), brine (50 mL), dried over anhydrous NaSO4, filtered and concentrated. The obtained crude compound was purified by CC using 10% ethyl acetate in PE as eluent to afford benzyl 2-(3-fluoro-4-((2-methoxyethoxy)methyl)phenyl)acrylate (1.4 g, 25%) as pale brown oil (TLC solvent system: 30% EtOAc-PE; Rf: 0.4).

Workup

  1. customwas deoxygenated
  2. customby purging Argon for 30 min at RT
  3. custompurging
  4. filtrationfiltered through a celite pad
  5. washwashed with ethyl acetate (2×25 mL)
  6. washThe filtrate was washed with water (2×100 mL), brine (50 mL)
  7. dry with materialdried over anhydrous NaSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe obtained crude compound
  11. customwas purified by CC

Sources & evidence

ORD record
ord-f060a4c9a84b42cc8cbbcd6040d4042a
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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