Cesium carbonate → Benzyl 2-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)acrylate

HRID 1842930Notes

Reaction equation

HRID 1842930 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16](B2OC(C)(C)C(C)(C)O2)=[CH:15][C:14]=1[F:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:36](=[CH2:47])[C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38]>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]>[CH2:1]([O:8][CH2:9][CH2:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:36](=[CH2:47])[C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:38])=[CH:15][C:14]=1[F:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 13443472Benzyl 2-bromoprop-2-enoateHCID 708164842-(4-((2-(Benzyloxy)ethoxy)methyl)-3-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane2×

Product 1

HCID 86672151Benzyl 2-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)acrylateYield 16.1%

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-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (16 g, 41.45 mmol), Cs2CO3 (40.5 g, 124.35 mmol) in DMF (150 ml) was deoxygenated by purging argon for 30 min at RT and Pd(dppf)Cl2 (1.69 g, 2.072 mmol) was added and purging continued. After 10 min, benzyl 2-bromoacrylate (15.7 g, 62.17 mmol) was added and stirred at 100° C. for 1 h until complete consumption of 2-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, as evidenced by TLC analysis. The reaction mixture was diluted with ethyl acetate (300 mL), filtered through a Celite and washed with ethyl acetate (2×50 mL). The combined filtrate was washed with water (3×200 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-(4-((2-(benzyloxy)ethoxy)methyl)-3-fluorophenyl)acrylate (2.8 g, 16%) as pale brown oil (TLC solvent system: 10% EtOAc in PE; Rf: 0.3).

Workup

  1. customwas deoxygenated
  2. customby purging argon for 30 min at RT
  3. custompurging
  4. filtrationfiltered through a Celite
  5. washwashed with ethyl acetate (2×50 mL)
  6. washThe combined filtrate was washed with water (3×200 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-c63bbc68b8894260aa39f1f756ff4e81
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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