Thionyl Chloride → HCID 18332155, compound
Reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[C:7]([CH:15]=[CH:16][C:17]=1[NH:18][C:19](=[O:27])[CH2:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:3])[CH3:2].C([O-])(=O)C.[Na+].S(Cl)([Cl:35])=O>C(OCC)(=O)C.ClCCl.CCCCCCC.O>[CH:1]([O:4][C:5]1[CH:6]=[C:7]([CH:15]=[CH:16][C:17]=1[NH:18][C:19](=[O:27])[CH:20]([Cl:35])[C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:8]([O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[O:9])([CH3:3])[CH3:2]Participants
Conditions
- Temperature
- -5 °C
Procedure
Compound D (130 g, 0.344 mol) and anhydrous sodium acetate (42.4 g, 0.516 mol) were combined in 300 miL dichloromethane in a 1 L three-neck flask fitted with a thermometer, addition funnel, and a gas inlet/outlet tube connected to a water aspirator acting as a gas scrubber. The stirred slurry was cooled to −5° C. in an ice/acetone bath under nitrogen. Thionyl chloride (46.5 g, 0.344 mol) was added dropwise to the stirred slurry, keeping the temperature below 5° C. TLC (50:45:5 heptane: dichloromethane:ethyl acetate) at the end of the addition showed some starting material. An additional 4 g thionyl chloride was added in 1 g portions, analyzing for residual Compound D after each addition. The final TLC showed only product and a trace of the dichlorinated product. The reaction mixture was slowly partitioned between 500 mL ethyl acetate and 1 L water containing 40 g sodium acetate. The aqueous layer was extracted with 200 ethyl acetate. The ethyl acetate layers were combined with 200 mL more ethyl acetate, and the solution extracted with 2×300 mL brine. The solution was dried over MgSO4, filtered, and evaporated to an orange-brown oil. Heptane (250 mL) was added and the solution evaporated to remove some residual acetic acid. The oil was chromatographed through 0.9 L silica gel in a 1 L sintered glass filter funnel. Heptane: dichloromethane (2:8) was used to remove most of the product, and then dichloromethane to remove the rest. The combined product fractions were evaporated to an orange oil. The oil was dissolved in 250 mL heptane, seeded, and left at room temperature overnight. The mixture was then cooled for 30 min in an ice bath and filtered to give 125 g colorless solid. The filtrate was evaporated and the residue crystallized from 35 mL cold heptane to give an additional 6.0 g off-white solid, pure by TLC. Total yield compound E: 131 g, 92%.
Workup
- customfitted with a thermometer, addition funnel, and a gas inlet/outlet tube
- customthe temperature below 5° C
- additionafter each addition
- customThe reaction mixture was slowly partitioned between 500 mL ethyl acetate and 1 L water containing 40 g sodium acetate
- extractionThe aqueous layer was extracted with 200 ethyl acetate
- extractionthe solution extracted with 2×300 mL brine
- dry with materialThe solution was dried over MgSO4
- filtrationfiltered
- customevaporated to an orange-brown oil
- additionHeptane (250 mL) was added
- customthe solution evaporated
- customto remove some residual acetic acid
- customThe oil was chromatographed through 0.9 L silica gel in a 1 L sintered glass
- filtrationfilter funnel
- customto remove most of the product
- customdichloromethane to remove the rest
- customThe combined product fractions were evaporated to an orange oil
- dissolutionThe oil was dissolved in 250 mL heptane
- temperatureThe mixture was then cooled for 30 min in an ice bath
- filtrationfiltered
Sources & evidence
- ORD record
- ord-42c633756be848558c52f192a82c17d2
- Source dataset
- uspto-grants-2001_12
- Patent number
- US06329130B1
Reaction notes
Loading…