Hexane → HCID 69108764, compound

HRID 749013Notes

Reaction equation

HRID 749013 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]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:38]=[CH:37][C:36](C=O)=[CH:35][CH:34]=2)=[CH:29][CH:28]=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:37]=[CH:38][C:33]([C:30]2[CH:31]=[CH:32][C:27]([CH2:26][CH:22]([NH:21][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])[C:23]([OH:25])=[O:24])=[CH:28][CH:29]=2)=[CH:34][CH:35]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 24758Sodium hydrideHCID 53413272TrimethylphosphonoacetateHCID 72551668HCID 72551668, compound

Product 1

HCID 69108764HCID 69108764, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
2.5 °C

Procedure

Sodium hydride (60% in mineral oil, 1.02 g, 26.0 mmol) was washed with anhydrous hexane (3×15 mL) under an atmosphere of argon. Dry THF (20 mL) was added and cooled to 0-5° C. A solution of trimethylphosphonoacetate (2.1 mL, 13.0 mmol) in dry THF (20 mL) was added dropwise to the above mixture with stirring. After about 5 min, a solution of the aldehyde 42 (4.3 g, 10.6 mmol) in dry THF (20 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 (25 mL) and further acidified to pH ˜2.0 with 2.0 M HCl. The THF was evaporated under reduced pressure and the resulting oily material was extracted with EtOAc (2×100 mL). The organic layer was extracted with water (3×75 mL), and brine (1×100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield the unsaturated ester 43 (4.6 g, 93%) as a crude product that was taken for the next step without further purification. 1H NMR (400 MHz, DMSO-d6): 12.66 (br, 1H), 7.80 (d, J=8.4 Hz, 2H), 7.72 (overlapped d, J=8.8 Hz, 2H), 7.70 (overlapped d, J=16.0 Hz, 1H), 7.36 (d, J=8.0 Hz, 2H), 7.18 (d, J=8.4 Hz, 1H), 6.69 (d, J=16.0 Hz, 1H), 4.13 (ddd, J=12.8, 10.4, and 4.8 Hz, 1H), 3.74 (s, 3H), 3.07 (dd, J=14.0 and 4.8 Hz, 1H), 2.88 (dd, J=13.6 and 10.0 Hz, 1H), 1.32 (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 (25 mL)
  5. customThe THF was evaporated under reduced pressure
  6. extractionthe resulting oily material was extracted with EtOAc (2×100 mL)
  7. extractionThe organic layer was extracted with water (3×75 mL), and brine (1×100 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3b818f23b16442af985f0bc3773a5f7b
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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