Cornforth reagent → HCID 90412768, compound
Reaction equation
[I:1][C:2]([I:34])=[CH:3][C@@H:4]1[O:8][C:7]([CH3:10])([CH3:9])[O:6][C@@H:5]1[CH:11]([OH:33])[CH2:12][O:13][C:14]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>ClCCl>[I:34][C:2]([I:1])=[CH:3][C@@H:4]1[O:8][C:7]([CH3:10])([CH3:9])[O:6][C@@H:5]1[C:11](=[O:33])[CH2:12][O:13][C:14]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
Compound 3 (38 kg, 55.7 mol) was dissolved in 100 L of dichloromethane and the solution was added into a 1000 L reactor charged with dichloromethane (500 L) followed by addition of 4 Å molecular sieves (42.9 kg) and neutral alumina (84 kg). To the stirred suspension at ambient temperature was added PDC (pyridinium dichromate) (25.1 kg, 66.8 mol) and the mixture was stirred 16 hours, until HPLC indicated complete conversion. The suspension was filtered using a centrifuge. The filtrate from the centrifuge was collected. The cake from the centrifuge (mainly alumina, molecular sieves and PDC residue) was washed with 2×100 L of methyl tert-butyl ether. The combined filtrate and wash was introduced into a 1000 L reactor and concentrated to dryness while keeping the heating below 50° C. To the residue was added 600 L of methyl tert-butyl ether, followed by 5 kg of activated carbon. The dark suspension was heated 1 hour at 60° C., then cooled down to 30° C. It was filtered through a pad of Celite to remove activated carbon. The filtrate was concentrated to dryness. The oily residue was diluted with 60 L of methanol and precipitates started to form. The thick suspension was stirred 1 hour at ambient temperature, then the precipitates were collected by filtration. The cake was washed twice with 50 L of petroleum ether and dried at 40° C. to afford 25.3 kg of 4 (yield 67%, purity>99%) as white solid. The Rf for 3 was ˜0.7, while Rf for 4 was ˜0.75 on silica gel TLC plate run in petroleum ether/ethyl acetate=4:1 and visualized under UV254 light or by using iodine treatment. 1H-NMR-(300 MHz, CDCl3) δ 7.23-7.48 (m, 15H), 6.80 (d, J=7.5 Hz, 1H), 4.75-4.85 (m, 2H), 3.95 (d, J=18.0 Hz, 1H), 3.80 (d, J=18.0 Hz, 1H), 1.41 (s, 3H), 1.34 (s, 3H); 13C-NMR (75 MHz, CDCl3) δ 203.22, 145.93 (—CH═CI2), 143.07, 128.62, 128.52, 128.21, 128.08, 127.43, 111.01, 87.57, 82.95, 80.00, 69.10, 26.85, 25.11, 18.53 (═CI2).
Workup
- additionthe solution was added into a 1000 L reactor
- additionfollowed by addition of 4 Å molecular sieves (42.9 kg) and neutral alumina (84 kg)
- filtrationThe suspension was filtered
- customThe filtrate from the centrifuge was collected
- washThe cake from the centrifuge (mainly alumina, molecular sieves and PDC residue) was washed with 2×100 L of methyl tert-butyl ether
- washThe combined filtrate and wash
- additionwas introduced into a 1000 L reactor
- concentrationconcentrated to dryness
- customthe heating below 50° C
- additionTo the residue was added 600 L of methyl tert-butyl ether
- temperaturecooled down to 30° C
- filtrationIt was filtered through a pad of Celite
- customto remove activated carbon
- concentrationThe filtrate was concentrated to dryness
- additionThe oily residue was diluted with 60 L of methanol
- customprecipitates
- customto form
- stirringThe thick suspension was stirred 1 hour at ambient temperature
- filtrationthe precipitates were collected by filtration
- washThe cake was washed twice with 50 L of petroleum ether
- customdried at 40° C.
Sources & evidence
- ORD record
- ord-8c6f4989ba454fd3972c9896f91c8ecb
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09150520B2
Reaction notes
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