Thionyl Chloride → HCID 178472528, compound

HRID 1879573Notes

Reaction equation

HRID 1879573 reaction equation
S(Cl)([Cl:3])=O.C(OC([NH:12][C@@:13]1([C:32]([O:34][C:35](C)(C)[CH3:36])=[O:33])[CH2:18][C@@H:17]([S:19][C:20]2[NH:24][CH:23]=[N:22][N:21]=2)[C@@H:16]2[C@H:14]1[C@H:15]2[C:25]([O:27][C:28](C)(C)[CH3:29])=[O:26])=O)(C)(C)C>C(O)C>[ClH:3].[NH2:12][C@@:13]1([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:18][C@@H:17]([S:19][C:20]2[NH:24][CH:23]=[N:22][N:21]=2)[C@@H:16]2[C@H:14]1[C@H:15]2[C:25]([O:27][CH2:28][CH3:29])=[O:26]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 178452940HCID 178452940, compound

Product 1

HCID 178472528HCID 178472528, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Add thionyl chloride (2.5 mL, 34.32 mmol) to a stirred solution of ditert-butyl (1R,2S,4R,5R,6R)-2-(tert-butoxycarbonylamino)-4-(4H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylate (2.1 g, 4.23 mmol) in ethanol (40 mL) at 0-5° C. dropwise over 5 minutes with caution (exothermic reaction). Remove the cooling bath and heat the reaction mixture at reflux temperature for 16 hours. Evaporate the volatiles and dry the residue under high vacuum for 7 hours to obtain a colorless foam of diethyl (1R,2S,4R,5R,6R)-2-amino-4-(4H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylate hydrochloride. Add then 2-(tert-butoxycarbonylamino)acetic acid (0.89 g, 5.07 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.93 g, 5.07 mmol) to a solution of diethyl (1R,2S,4R,5R,6R)-2-amino-4-(4H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylate hydrochloride in anhydrous N,N-dimethylformamide (20 mL) at room temperature then add diisopropylethylamine (2 mL, 11.47 mmol) and stir the resulting yellow solution under nitrogen for 18 hours. Concentrate the solvent and partition the residue between ethyl acetate (40 mL) and a saturated solution of sodium hydrogen carbonate in water (40 mL). Stir the mixture for 20 minutes, separate the layers and extract the aqueous layer with more ethyl acetate (40 mL). Combine the organics layers, dry on sodium sulfate and concentrate to dryness. Purify the residue by flash chromatography eluting with ethyl acetate: iso-hexane (80:20 to 100:0) to give the title compound as a colorless solid (2.42 g, 4.86 mmol). MS (m/z): 498 (M+1), 520 (M+23).

Workup

  1. customwith caution (exothermic reaction)
  2. customRemove the cooling bath
  3. temperatureheat the reaction mixture
  4. temperatureat reflux temperature for 16 hours
  5. customEvaporate the volatiles
  6. customdry the residue under high vacuum for 7 hours

Sources & evidence

ORD record
ord-352573f5c7f24d848bc9706c743256e1
Source dataset
uspto-grants-2012_11
Patent number
US08318184B2

Reaction notes

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