Sodium hydride → HCID 67727659, compound

HRID 2258568Notes

Reaction equation

HRID 2258568 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:5]=1[CH:6]=O.[Br-].[CH:15]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[CH2:16].[C:36]1(=[O:46])[NH:40][C:39](=[O:41])[C:38]2=[CH:42][CH:43]=[CH:44][CH:45]=[C:37]12.[K]>C1COCC1.C(O)C>[F:3][C:4]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:5]=1/[CH:6]=[CH:15]\[CH2:16][N:40]1[C:36](=[O:46])[C:37]2[C:38](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:39]1=[O:41]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 2723893Ethenyl(triphenyl)phosphanium bromideHCID 27348722-Fluoro-5-methoxybenzaldehydeHCID 24194345Phthalimide potassium salt

Product 1

HCID 67727659HCID 67727659, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

A cold (0° C.) suspension of NaH (3.88 g, 97 mmol) and 2-fluoro-5-methoxy benzaldehyde (10.0 g, 65 mmol) in THF (400 mL) was treated with an admix of vinyltriphenylphosphonium bromide (31.2 g, 84.5 mmol) and potassium phthalimide (15.65 g, 84.5 mmol) under N2. The reaction was then slowly heated to 45° C. for 1 h, followed by standing at ambient temperature for 18 h. The dark solution was quenched with 5% citric acid (25 mL), then diluted with H2O (800 mL). The suspension was extracted with EtOAc (3×), the organics were combined and washed with 5% citric acid (3×), H2O (1×), brine, and dried over K2CO3. The crude oil was flashed through a plug of silica gel (toluene-2%MeOH/toluene) to afford pure material as a cis/trans mix (60/40, based on NMR). The cis compound was isolated by recrystallization from hot ethanol to give the titled cis isomer, 2.08 g, as a white solid, 10%: 1H NMR (300 MHz, CDCl3) δ 3.82 (s, 3H), 4.48 (m, 2H), 5.76 (m, 1H), 6.56 (d, J=12.0 Hz, 1H), 6.70-7.05 (m, 3H), 7.68-7.86 (m, 4H); MS m/e 311; Analysis calc'd for C18H14NO3F 0.12(EtOH): C, 68.95; H, 4.78; N, 4.37; found: C, 69.23; H, 4.92; N, 4.37.

Workup

  1. customThe dark solution was quenched with 5% citric acid (25 mL)
  2. additiondiluted with H2O (800 mL)
  3. extractionThe suspension was extracted with EtOAc (3×)
  4. washwashed with 5% citric acid (3×), H2O (1×), brine
  5. dry with materialdried over K2CO3
  6. customto afford pure material as a cis/trans
  7. additionmix (60/40, based on NMR)
  8. customto give the titled cis isomer, 2.08 g

Sources & evidence

ORD record
ord-23cca79c0ba74453abcf7bed3722b556
Source dataset
uspto-grants-1997_08
Patent number
US05661185

Reaction notes

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