Tetrahydrofuran → (3aR,6aS)-2-Hydroxy-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-5-carbaldehyde

The solution of succinaldehyde 8 from the first step (109.5 g, 1.272 mol) in 2-MeTHF was stirred at r.t. (S)-Proline (2.93 g, 25.4 mmol, 0.02 eq.) was added as a solid and the reaction stirred at r.t. for 20 h. THF (650 ml) was added, followed by [Bn2NH2][OCOCF3] (8.43 g, 25.4 mmol, 0.02 eq.). The reaction was stirred for a further 14 h. Celite (60 g) was added to the reaction and the volume of the reaction mixture was reduced by ¾ under reduced pressure. tert-Butyl methyl ether (TBME) (an equal volume to the volume of THF/2-MeTHF removed) was added slowly (over ˜15 mins) and with vigorous stirring of the mixture. The mixture was stirred for 20 min before filtration of the resulting solids (through a sinter funnel). The solids were washed with TBME (3×150 ml) and the filtrate was concentrated under reduced pressure. The material was purified by column chromatography (˜600 g silica), eluting with petrol/EtOAc (6:4 to 5:5), to give the lactol 7 (as an approximately 2:1 mixture of diastereoisomers), as a brown oil.

1. additionwas added as a solid
2. stirringThe reaction was stirred for a further 14 h
3. additionCelite (60 g) was added to the reaction
4. customtert-Butyl methyl ether (TBME) (an equal volume to the volume of THF/2-MeTHF removed)
5. additionwas added slowly (over ˜15 mins)
6. stirringwith vigorous stirring of the mixture
7. stirringThe mixture was stirred for 20 min before filtration of the resulting solids (through a sinter funnel)
8. washThe solids were washed with TBME (3×150 ml)
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe material was purified by column chromatography (˜600 g silica)
11. washeluting with petrol/EtOAc (6:4 to 5:5)

ORD 기록

ord-3529beb7412f4496ba184de4c98d500e

출처 데이터셋

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09242954B2