Tetrabutylammonium Fluoride → HCID 58573529, compound

HRID 932264Notes

Reaction equation

HRID 932264 reaction equation
[CH2:1]([C@:4]1([CH2:47][CH2:48][O:49][CH2:50][C:51]2[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=2)[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:44][CH3:45])[CH2:25][O:26][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[C:5]1=[O:46])[CH:2]=[CH2:3].C([C@@]1(CCOCC2C=CC(OC)=CC=2)C[C@H](C2C=CC=C(Cl)C=2)[C@@H](C2C=CC(Cl)=CC=2)N([C@@H](CC)CO[Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)C1=O)C=C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH2:1]([C@:4]1([CH2:47][CH2:48][O:49][CH2:50][C:51]2[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=2)[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:44][CH3:45])[CH2:25][OH:26])[C:5]1=[O:46])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 67999144HCID 67999144, compoundHCID 67999596HCID 67999596, compound

Product 1

HCID 58573529HCID 58573529, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of a mixture of (3R,5R,6S)-3-allyl-1-((S)-1-((tert-butyldiphenylsilyl)oxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-(2-((4-methoxybenzyl)oxy)ethyl)piperidin-2-one and (3S,5R,6S)-3-allyl-1-((S)-1-((tert-butyldiphenylsilyl)oxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-(2-((4-methoxybenzyl)oxy)ethyl)piperidin-2-one (19.23 g, 23.03 mmol; Example 408, Step A) in THF (92 ml) at rt was slowly added a solution of TBAF (1.0M in THF, 34.5 ml, 34.5 mmol). The reaction was monitored by LCMS, and when judged complete was concentrated under reduced pressure (no heat), then diluted in 400 mL of EtOAc. HCl (1N, 150 ml) was added. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organics were washed several times with water, dried over MgSO4, filtered, and the filtrate was concentrated. Purification by chromatography on silica gel (eluent: 10 to 20% EtOAc/hexane, gradient elution over 30 min) provided the title compound along with its C3 epimer as a clear, colorless foam. Individual steroisomers were separated by chiral HPLC (flowrate: 120 ml/min, 1 g per injection, on a Chiralcel® OD-H 5 cm I.D.×50 cm, 20 μm column; Daicel Chemical Industries LTD, using 6% isopropyl alcohol/hexane as the eluent) to give the title compound as the first eluting isomer (tR=11-23 min) as a clear, viscous oil.

Workup

  1. concentrationjudged complete was concentrated under reduced pressure (
  2. temperatureno heat),
  3. additionthen diluted in 400 mL of EtOAc
  4. additionHCl (1N, 150 ml) was added
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc
  7. washThe combined organics were washed several times with water
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customPurification by chromatography on silica gel (eluent: 10 to 20% EtOAc/hexane, gradient elution over 30 min)

Sources & evidence

ORD record
ord-f6a47cca73ec44b287aab4ed6d4320d2
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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