Hexane → 3-{4-[4-(Tert-butoxycarbonylaminocarboxymethyl)-phenoxy]-phenyl}-acrylic acid methyl ester

HRID 749001Notes

Reaction equation

HRID 749001 reaction equation
[H-].[Na+].C[C:4](P(OC)(O)=O)([C:6]([O-:8])=[O:7])[CH3:5].[C:14]([O:18][C:19]([NH:21][CH:22]([C:26]1[CH:31]=[CH:30][C:29]([O:32][C:33]2[CH:38]=[CH:37][C:36](C=O)=[CH:35][CH:34]=2)=[CH:28][CH:27]=1)[C:23]([OH:25])=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15].[CH3:41]CCCCC>C1COCC1>[CH3:41][O:8][C:6](=[O:7])[CH:4]=[CH:5][C:36]1[CH:35]=[CH:34][C:33]([O:32][C:29]2[CH:30]=[CH:31][C:26]([CH:22]([NH:21][C:19]([O:18][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:20])[C:23]([OH:25])=[O:24])=[CH:27][CH:28]=2)=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 24758Sodium hydrideHCID 53413272TrimethylphosphonoacetateHCID 59751112Tert-butoxycarbonylamino-[4-(4-formylphenoxy)-phenyl]-acetic acid

Product 1

HCID 692266383-{4-[4-(Tert-butoxycarbonylaminocarboxymethyl)-phenoxy]-phenyl}-acrylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
2.5 °C

Procedure

Sodium hydride (60% in mineral oil, 4.03 g, 100.0 mmol) was washed with anhydrous hexane (3×50 mL) under an atmosphere of argon. Dry THF (200 mL) was added and cooled to 0-5° C. A solution of trimethylphosphonoacetate (8.2 mL, 50.0 mmol) in dry THF (35 mL) was added dropwise to the above mixture with stirring. After about 5 min, a solution of the aldehyde 29 (17.0 g, 46.0 mmol) in dry THF (35 mL) was added and the reaction mixture was then brought up to room temperature and stirred. After 30 min, the clear reaction mixture was quenched with 10% citric acid (50 mL) and further acidified to pH ˜2.0 with 2.0 M HCl. THF was evaporated under reduced pressure and the resulting oily material was extracted with EtOAc (2×400 mL). The organic layer was extracted with water (3×500 mL), and brine (1×500 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield the unsaturated ester 30 (20.0 g, quantitative yield) as a crude product that was taken for the next step without further purification. 1H NMR (400 MHz, DMSO-d6): 12.9 (br, 1H), 7.75 (d, J=8.8 Hz, 2H), 7.65 (d, J=12.0 Hz, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.05 (d, J=8.8 Hz, 2H), 7.01 (d, J=8.8 Hz, 2H), 6.56 (d, J=12.0 Hz, 1H), 5.12 (d, J=8.0 Hz, 1H), 3.72 (s, 3H), 1.40 (s, 9H).

Workup

  1. customwas then brought up to room temperature
  2. stirringstirred
  3. waitAfter 30 min
  4. customthe clear reaction mixture was quenched with 10% citric acid (50 mL)
  5. customTHF was evaporated under reduced pressure
  6. extractionthe resulting oily material was extracted with EtOAc (2×400 mL)
  7. extractionThe organic layer was extracted with water (3×500 mL), and brine (1×500 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-66abc0d4995942888c6887b0112bcfe1
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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