Ethyl 2-bromobenzoate → Ethyl 2-(3-(3-(((2-tetrahydropyranyl)oxy)methyl)phenyl)-3-oxopropyl)benzoate

HRID 2226982Notes

Reaction equation

HRID 2226982 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][C:9]1[CH:10]=[C:11]([CH:15]([OH:18])[CH:16]=[CH2:17])[CH:12]=[CH:13][CH:14]=1.Br[C:20]1[CH:30]=[CH:29][CH:28]=[CH:27][C:21]=1[C:22]([O:24][CH2:25][CH3:26])=[O:23].[Li+].[Cl-].[Li]OC(C)=O.O.O>CN(C=O)C>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][C:9]1[CH:10]=[C:11]([C:15](=[O:18])[CH2:16][CH2:17][C:27]2[CH:28]=[CH:29][CH:30]=[CH:20][C:21]=2[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 80186Ethyl 2-bromobenzoateHCID 433294Lithium ChlorideHCID 190029401-(3-(((2-Tetrahydropyranyl)oxy)methyl)phenyl)-2-propen-1-olHCID 178526966lithium;acetate;dihydrate

Product 1

HCID 22417658Ethyl 2-(3-(3-(((2-tetrahydropyranyl)oxy)methyl)phenyl)-3-oxopropyl)benzoateYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

The allylic alcohol of Step 10 (24.8 g, 100 mmol) and ethyl 2-bromobenzoate (25.2 g, 110 mmol) were dissolved in DMF (200 mL). LiCl (4.2 g, 100 mmol), LiOAc.2H2O (25.5 g, 250 mmol) and n-Bu4N+Cl- (55 g, 200 mmol) were added and the resulting mixture was degassed three times. Pd(OAc)2 (1 g) was then added and the mixture was degassed three more times before heating it at 100° C. with stirring for 1 hour. After cooling to r.t., the reaction mixture was poured onto H2O (600 mL), 10% aq. NaHCO3 (200 mL) and Et2O. The crude product was extracted with Et2O (2×), washed with H2O and brine, and dried over Na2SO4 before concentrating in vacuo. Purification on a short silica gel column (20% EtOAc in hexanes) gave 34 g (86%) of the title compound. 1H NMR (CD3COCD3): δ8.02 (1H, br s), 7.92 (1H, d), 7.88 (1H, d), 7.65 (1H, d), 7.50 (3H, m), 7.32 (1H, br t), 4.8 (1H, d), 4.70 (1H, br s), 4.54 (1H, d), 4.3 (2H, q), 3.82 (1H, m), 3.50 (1H, m), 3.35 (2H, m), 1.9-1.45 (8H, m), 1.32 (3H, t).

Workup

  1. customthe resulting mixture was degassed three times
  2. additionPd(OAc)2 (1 g) was then added
  3. customthe mixture was degassed three more times
  4. temperatureAfter cooling to r.t.
  5. additionthe reaction mixture was poured onto H2O (600 mL), 10% aq. NaHCO3 (200 mL) and Et2O
  6. extractionThe crude product was extracted with Et2O (2×)
  7. washwashed with H2O and brine
  8. dry with materialdried over Na2SO4
  9. concentrationbefore concentrating in vacuo
  10. customPurification on a short silica gel column (20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-7ea2bd898ac5466bb041c2ad4239b64a
Source dataset
uspto-grants-1994_09
Patent number
US05350760

Reaction notes

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