1,2-Dichloroethane → HCID 58017527, compound

HRID 1642763Notes

Reaction equation

HRID 1642763 reaction equation
[O:1]1[CH2:5][CH2:4][C@@H:3]([C:6]([O:8]CC)=O)[N:2]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[OH-].[Li+].Cl.[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([N:30]2[CH:34]=[N:33][N:32]=[N:31]2)=[C:26]([CH:29]=1)[CH2:27][NH2:28].OC1C2N=NNC=2C=CC=1.C(Cl)CCl.CN1CCOCC1>C(#N)C.O.C(Cl)Cl>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([N:30]2[CH:34]=[N:33][N:32]=[N:31]2)=[C:26]([CH:29]=1)[CH2:27][NH:28][C:6]([C@@H:3]1[CH2:4][CH2:5][O:1][N:2]1[C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])=[O:8]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 3939Lithium HydroxideHCID 79724-MethylmorpholineHCID 57473410HCID 57473410, compoundHCID 58017546HCID 58017546, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 58017527HCID 58017527, compoundYield 87.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-tert-butyl 3-ethyl (3S)-isoxazolidine-2,3-dicarboxylate (245 mg, 1.00 mmol) in acetonitrile (2.5 mL) and water (1 mL) was added lithium hydroxide (1 M in water, 1.00 mL, 1.00 mmol) and the mixture was stirred at rt for 30 min. To this solution was added 5-chloro-2-tetrazol-1-yl-benzylamine hydrochloride (295 mg, 1.20 mmol, prepared as described in J. Med. Chem. 2004, 47, 2995), hydroxybenzotriazole (135 mg, 1.00 mmol, as a 20% solution in water, ca 0.65 mL), EDC (288 mg, 1.50 mmol) and NMM (202 mg, 2.00 mmol). The resulting mixture was stirred at rt over night, then diluted with DCM and washed with 1 M HCl and saturated sodium hydrogen carbonate. The organic phase was dried, filtered, evaporated and purified by flash chromatography (DCM/EtOAc gradient from 4:1 to 1:1) to give tert-butyl (3S)-3-{[5-chloro-2-(1H-tetrazol-1-yl)benzyl]carbamoyl}isoxazolidine-2-carboxylate (357 mg, 87%) as an oil.

Workup

  1. stirringThe resulting mixture was stirred at rt over night
  2. washwashed with 1 M HCl and saturated sodium hydrogen carbonate
  3. customThe organic phase was dried
  4. filtrationfiltered
  5. customevaporated
  6. custompurified by flash chromatography (DCM/EtOAc gradient from 4:1 to 1:1)

Sources & evidence

ORD record
ord-b4e73c52171e4651b39f74f4fc2f4cb8
Source dataset
uspto-grants-2012_02
Patent number
US08119673B2

Reaction notes

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