Hydrochloric Acid → Methyl(1R,2R,5S,6S)-6-fluoro-2-hydroxy-4-oxobicyclo[3.1.0]hexane-6-carboxylate

Temperature

22 °C

The above organic layer, containing TBS-ketone 6 (6.83 mol) was warmed to 22° C. and 1 M HCl (1.37 L) was added. The mixture was stirred at 22-24° C. for 3.5 h until all TBS groups were removed. To the mixture was added saturated sodium bicarbonate solution (4.8 L). The mixture was stirred for 15 min, diluted with isopropyl acetate (20 L), and the organic layer was separated. The aqueous layer was back extracted with isopropyl acetate (6 L). The combined organic solutions were concentrated to dryness and the compound was purified by silica gel chromatography in a filter pot (first eluted with 30% MTBE in hexane, then MTBE alone) to give compound 7 as an off white crystal. Analytical pure sample was obtained by further flash silica gel column as colorless crystals: mp 61-62° C.; 1H NMR (400 MHz, CDCl3): δ 4.92 (br s, 1H), 3.85 (s, 3H); 2.86 (dd, J=6.2, 2.1 Hz, 1H), 2.71 (d, J=6.2 Hz, 1H), 2.61 (dt, J=19.4, 5.7 Hz, 1H), 2.59 (br s, 1H), 2.30 (dd, J=19.4, 3.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 206.9, 167.0 (d, J=26.2 Hz), 79.0 (d, J=246.6 Hz), 67.0 (d, J=3.1 Hz), 53.5, 46.8 (d, J=4.2 Hz), 41.6 (d, J=11.8 Hz), 39.4 (d, J=13.1 Hz); 19F NMR (376 MHz, CDCl3): δ −210.6; [α]D25=+77 (c 0.50, CH3OH).

1. customwere removed
2. additionTo the mixture was added saturated sodium bicarbonate solution (4.8 L)
3. stirringThe mixture was stirred for 15 min
4. additiondiluted with isopropyl acetate (20 L)
5. customthe organic layer was separated
6. extractionThe aqueous layer was back extracted with isopropyl acetate (6 L)
7. concentrationThe combined organic solutions were concentrated to dryness
8. customthe compound was purified by silica gel chromatography in a filter pot (
9. washfirst eluted with 30% MTBE in hexane

ORD record

ord-59b86e76222d4fe4aed514a610acf015

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07786314B2