Ethyl Acetate → HCID 118353311, compound

HRID 921060Notes

Reaction equation

HRID 921060 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:15][CH2:16][CH:17]2[CH2:19][CH2:18]2)=[C:6](/[CH:8]=[CH:9]/[C:10](OCC)=[O:11])[CH:7]=1.[H-].C([Al+]CC(C)C)C(C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+].CCOC(C)=O>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:15][CH2:16][CH:17]2[CH2:18][CH2:19]2)=[C:6](/[CH:8]=[CH:9]/[CH2:10][OH:11])[CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9357Potassium Sodium TartrateHCID 21225700DiisobutylaluminumhydrideHCID 118361661HCID 118361661, compound

Product 1

HCID 118353311HCID 118353311, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

To (E)-ethyl 3-(5-bromo-2-(cyclopropylmethoxy)phenyl)acrylate (S6) (3.78 g, 11.6 mmol, 1.00 equiv) in PhMe (30 mL) in a flame-dried round-bottom flask under a N2 atmosphere at −78 ° C. was added a 1.0 M solution of diisobutylaluminum hydride (DIBAL-H) in PhMe (26 mL, 26 mmol, 2.2 equiv) in 6 portions dropwise every 10 minutes for 1 hour. The reaction was warmed to 0 ° C. over 2 hours and then warmed to 23 ° C. and stirred at this temperature for 1 hour. The reaction mixture was poured onto a concentrated aqueous Rochelle's salt (potassium sodium tartrate) solution (400 mL). EtOAc (400 mL) was added and the mixture was stirred for 3 hour until two liquid phases separated cleanly. The phases were partitioned and the aqueous phase was extracted from with EtOAc (300 mL). The organic phases were combined and washed with brine (200 mL), dried with Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with a gradient of 10-25% EtOAc in hexanes (v/v) to afford 2.77 g of the title compound as a colorless solid (84% yield). Rf=0.15 (hexanes/EtOAc 6:1 (v/v)). NMR Spectroscopy: 1H NMR (500 MHz, CDCl3, 23 ° C., δ): 7.53 (d, J=2.4 Hz, 1H), 7.26 (dd, J=8.8, 2.4 Hz, 1H), 6.88 (d, J=16.1 Hz, 1H), 6.69 (d, J=8.8 Hz, 1H), 6.39 (dt, J=16.1, 5.9 Hz, 1H), 4.33 (br dd, J=4.6, 4.6 Hz, 2H), 3.79 (d, J=6.8 Hz, 2H), 1.71 (br t, J=5.1 Hz, 1H), 1.31-1.23 (m, 1H), 0.68-0.58 (m, 2H), 0.38-0.30 (m, 2H). 13C NMR (125 MHz, CDCl3, 23 ° C., δ): 155.4, 131.2, 130.5, 129.7, 128.2, 125.0, 114.2, 113.2, 73.7, 64.1, 10.3, 3.4. HRMS-FIA (m/z): calcd for C13H15BrNaO2 [M+Na]+, 305.0153; found, 305.0123.

Workup

  1. temperaturewarmed to 23 ° C.
  2. stirringthe mixture was stirred for 3 hour until two liquid phases
  3. customseparated cleanly
  4. customThe phases were partitioned
  5. extractionthe aqueous phase was extracted from with EtOAc (300 mL)
  6. washwashed with brine (200 mL)
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on silica gel
  10. washeluting with a gradient of 10-25% EtOAc in hexanes (v/v)

Sources & evidence

ORD record
ord-c8e98454901a4d1c9a0cda355781fb00
Source dataset
uspto-grants-2016_03
Patent number
US09273083B2

Reaction notes

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