Sodium hydride → Methyl 5-(3-((1R,2R,3R,5R)-2-((R,E)-7-(tert-butyldimethylsilyloxy)-3-oxooct-1-enyl)-5-chloro-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylate

HRID 1694325Notes

Reaction equation

HRID 1694325 reaction equation
[H-].[Na+].[Si:3]([O:10][C@H:11]([CH3:24])[CH2:12][CH2:13][CH2:14][C:15](=[O:23])[CH2:16]P(=O)(OC)OC)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[Cl:25][C@H:26]1[C@H:30]([CH2:31][CH2:32][CH2:33][C:34]2[S:38][C:37]([C:39]([O:41][CH3:42])=[O:40])=[CH:36][CH:35]=2)[C@@H:29]([CH:43]=O)[C@H:28]([O:45][CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][O:47]2)[CH2:27]1>C1COCC1>[Si:3]([O:10][C@H:11]([CH3:24])[CH2:12][CH2:13][CH2:14][C:15](=[O:23])/[CH:16]=[CH:43]/[C@H:29]1[C@H:28]([O:45][CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][O:47]2)[CH2:27][C@@H:26]([Cl:25])[C@@H:30]1[CH2:31][CH2:32][CH2:33][C:34]1[S:38][C:37]([C:39]([O:41][CH3:42])=[O:40])=[CH:36][CH:35]=1)([C:6]([CH3:7])([CH3:8])[CH3:9])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 14166335dimethyl (6R)-6-{[tert-butyl(dimethyl)silyl]oxy}-2-oxoheptylphosphonateHCID 57845631Methyl 5-(3-((1R,2R,3R,5R)-5-chloro-2-formyl-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylate

Product 1

HCID 57734100Methyl 5-(3-((1R,2R,3R,5R)-2-((R,E)-7-(tert-butyldimethylsilyloxy)-3-oxooct-1-enyl)-5-chloro-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylateYield 60.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
25 °C

Procedure

To a suspension of 54 mg of sodium hydride (60% oil dispersion, 1.35 mmol) in 1 ml of THF at 0° C. was added a solution of dimethyl (6R)-6-{[tert-butyl(dimethyl)silyl]oxy}-2-oxoheptylphosphonate 5 (552 mg, 1.57 mmol) in 1 mL THF. The mixture was stirred at 0° C. for 30 min before a solution of aldehyde 7 (460 mg, 1.1 mmol) in 1 ml of THF was added dropwise. The syringe containing the aldehyde was rinsed with 2 mL of THF to complete the addition and the mixture was stirred at 25° C. for 2.5 h. The reaction was worked up with addition of saturated aqueous ammonium chloride (50 mL) and the aqueous layer was extracted with ethyl acetate (2×75 mL). The ethyl acetate layers were combined and washed with brine, dried over 30 g of anhydrous sodium sulfate, filtered and concentrated in vacuo to yield 920 mg of crude products. Flash chromatographic purification using a 24 g silica gel cartridge eluted with 10% EtOAc-hexanes yielded 430 mg (60%) of purified enone 8; 1H NMR (CDCl3): 0.05 (s, 6H), 0.88 (s, 9H), 1.12 (d, J=6.3 Hz, 3H), 1.37-1.80 (m, 14H), 2.00 (m, 1H), 2.20 (m, 1H), 2.34 (m, 1H), 2.53 (m, 1H), 2.54 (t, J=7.2 Hz, 2H), 2.83 (m, 2H), 3.45 (m, 1H), 3.80 (m, 2H), 3.86 (s, 3H), 4.02 (m, 1H), 4.17 (m, 1H), 4.57 (m, 1H), 6.15 (m, 1H), 6.77 (m, 1H), 7.62 (d, J=3.9 Hz).

Workup

  1. additionwas added dropwise
  2. washwas rinsed with 2 mL of THF
  3. additionthe addition
  4. additionThe reaction was worked up with addition of saturated aqueous ammonium chloride (50 mL)
  5. extractionthe aqueous layer was extracted with ethyl acetate (2×75 mL)
  6. washwashed with brine
  7. dry with materialdried over 30 g of anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield 920 mg of crude products
  11. customFlash chromatographic purification
  12. washeluted with 10% EtOAc-hexanes

Sources & evidence

ORD record
ord-e3132dfbf34145c2b1f25447d76d711c
Source dataset
uspto-grants-2012_04
Patent number
US08158676B2

Reaction notes

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