Dimethyl Sulfoxide → HCID 86661742, compound

HRID 1961554Notes

Reaction equation

HRID 1961554 reaction equation
CS(O[C:6]1([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH2:33][C:32]([C:38]4[CH:43]=[C:42]([Cl:44])[C:41]([Cl:45])=[C:40]([Cl:46])[CH:39]=4)([C:34]([F:37])([F:36])[F:35])[O:31][N:30]=3)=[CH:25][CH:24]=2)[CH2:9][N:8]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7]1)(=O)=O.[N-:47]=[N+:48]=[N-:49].[Na+].CS(C)=O>C(Cl)Cl.C([O-])(O)=O.[Na+]>[N:47]([C:6]1([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH2:33][C:32]([C:38]4[CH:43]=[C:42]([Cl:44])[C:41]([Cl:45])=[C:40]([Cl:46])[CH:39]=4)([C:34]([F:37])([F:36])[F:35])[O:31][N:30]=3)=[CH:25][CH:24]=2)[CH2:9][N:8]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7]1)=[N+:48]=[N-:49]

Participants

6

Reactant 3

HCID 679Dimethyl SulfoxideHCID 33557Sodium AzideHCID 86661743HCID 86661743, compound

Product 1

HCID 86661742HCID 86661742, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 1.19 grams (1.88 mmole, 1.0 eq) of 1-benzhydryl-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)azetidin-3-ol in 17 mL of CH2Cl2 was added 500 μL (2.8 mmole, 1.5 eq) of diisopropyl-ethylamine, neat via syringe, followed by 438 mg (2.5 mmole, 1.3 eq) of methylsulfonic anhydride solid. After stirring 3.5 hours at room temperature an aliquot of the reaction mixture was placed in 1.0 mL of methanol and analyzed via LC/MS. The chromatograph indicated the starting material was consumed. The reaction with diluted with 20 mL of CH2Cl2 and 20 mL of saturated NaHCO3 solution. After stirring for 2 hours the layers were separated via a Biotage Phase Separator cartridge. The organic layer was concentrated under reduced pressure to give 1.29 grams (96% yield) of intermediate 1-benzhydryl-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)azetidin-3-yl methanesulfonate as light yellow solid. A 227 mg sample of 1-benzhydryl-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)azetidin-3-yl methanesulfonate (0.35 mmole, 1.0 eq) and 72.1 mg of sodium azide (1.1 mmole, 3.1 eq) were weighed into a 100 mL flask, to this was added 3 mL of anhydrous DMSO. After stirring for 1.5 hours at room temperature the reaction was diluted with 30 mL of CH2Cl2 and 15 mL of saturated NaHCO3 solution. After stirring this mixture for 1 hour the layers were separated via a Biotage Phase Separator cartridge. The water layer was rinsed with additional CH2Cl2 and the combined organic layers were concentrated by evaporation utilizing a stream of N2 gas. The resulting crude oil was purified via silica gel column chromatography eluting with 100% CH2Cl2. Evaporation of the appropriate fractions gave 144.5 mg of product, 3-(4-(3-azido-1-benzhydrylazetidin-3-yl)phenyl)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole, (63% yield) as a glassy yellow solid. ms 656 [M+H], HPLC retention time: 3.600 minutes.

Workup

  1. stirringAfter stirring this mixture for 1 hour the layers
  2. customwere separated via a Biotage Phase Separator cartridge
  3. washThe water layer was rinsed with additional CH2Cl2
  4. concentrationthe combined organic layers were concentrated by evaporation
  5. customThe resulting crude oil was purified via silica gel column chromatography
  6. washeluting with 100% CH2Cl2
  7. customEvaporation of the appropriate fractions

Sources & evidence

ORD record
ord-07eb4a1d475641d8a67d52c56713d6e2
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

Loading…