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

Temperatur

100 °C

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).

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)

ORD-Eintrag

ord-7ea2bd898ac5466bb041c2ad4239b64a

Quelldatensatz

uspto-grants-1994_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05350760