TBAF tetrahydrofuran → Methyl 5-(3-((1R,2R,3R,5R)-5-chloro-2-((3S,7R,E)-3,7-dihydroxyoct-1-enyl)-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylate

HRID 1694327Notes

Reaction equation

HRID 1694327 reaction equation
[Si]([O:8][C@H:9]([CH3:42])[CH2:10][CH2:11][CH2:12][C@H:13]([OH:41])/[CH:14]=[CH:15]/[C@H:16]1[C@H:20]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH2:19][C@@H:18]([Cl:28])[C@@H:17]1[CH2:29][CH2:30][CH2:31][C:32]1[S:36][C:35]([C:37]([O:39][CH3:40])=[O:38])=[CH:34][CH:33]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C1COCC1>[Cl:28][C@H:18]1[C@H:17]([CH2:29][CH2:30][CH2:31][C:32]2[S:36][C:35]([C:37]([O:39][CH3:40])=[O:38])=[CH:34][CH:33]=2)[C@@H:16](/[CH:15]=[CH:14]/[C@@H:13]([OH:41])[CH2:12][CH2:11][CH2:10][C@H:9]([OH:8])[CH3:42])[C@H:20]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH2:19]1

Participants

4

Reactant 2

HCID 11078149TBAF tetrahydrofuranHCID 57734084Methyl 5-(3-((1R,2R,3R,5R)-2-((3S,7R,E)-7-(tert-butyldimethylsilyloxy)-3-hydroxyoct-1-enyl)-5-chloro-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylate

Product 1

HCID 57734132Methyl 5-(3-((1R,2R,3R,5R)-5-chloro-2-((3S,7R,E)-3,7-dihydroxyoct-1-enyl)-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of silyl ether 9 (325 mg, 0.51 mmol) in 1 mL of THF was stirred at 30° C. with 2 mL of 1.0M TBAF/THF in a vial for 7.5 h. TLC indicated starting material was mostly desilylated and the reaction was concentrated in vacuo. The residual crude products were taken up in 50 mL of ethyl acetate and washed sequentially with saturated aqueous ammonium chloride (50 mL), brine (50 mL), and dried over 10 g of anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo. The residual products were purified by preparative layer chromatography on 2×2 mm thick silica gel plates eluted in EtOAc (Rf=0.5). Extraction of the major band yielded 214 mg (80%) of pure diol 10 as an oil; 1H NMR (CDCl3): 1.18 (d, J=6 Hz, 3H), 1.38-1.68 (m, 11H), 1.66-2.37 (m, 9H), 2.84 (t, J=7.2 Hz, 2H), 3.47 (m, 1H), 3.79 (m, 1H), 3.86 (s, 3H), 3.98 (p, J=7.5 Hz, 1H), 4.09 (m, 2H), 4.63 (dt, J=3, 27 Hz, 2H), 5.58 (m, 2H), 6.78 (dd, J=0.6, 3.6 Hz, 1H), 7.62 (d, J=3.6 Hz, 1H).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. washwashed sequentially with saturated aqueous ammonium chloride (50 mL), brine (50 mL)
  3. dry with materialdried over 10 g of anhydrous sodium sulfate
  4. filtrationThe mixture was filtered
  5. concentrationconcentrated in vacuo
  6. customThe residual products were purified by preparative layer chromatography on 2×2 mm thick silica gel plates
  7. washeluted in EtOAc (Rf=0.5)
  8. extractionExtraction of the major band

Sources & evidence

ORD record
ord-22a68ab450b24ef2b31a296ef76a90e0
Source dataset
uspto-grants-2012_04
Patent number
US08158676B2

Reaction notes

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