Hydrochloric Acid → (S)-1-(1,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl)-azetidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide

HRID 389862Notes

Reaction equation

HRID 389862 reaction equation
[O:1]=[S:2]1(=[O:11])[CH2:7][CH2:6][N:5]([C:8](Cl)=[O:9])[CH2:4][CH2:3]1.[C:12]([C:16]1[CH:20]=[C:19]([NH:21][C:22]([C@@H:24]2[CH2:27][CH2:26][NH:25]2)=[O:23])[O:18][N:17]=1)([CH3:15])([CH3:14])[CH3:13].Cl.C(N(CC)C(C)C)(C)C>C1COCC1.ClCCl>[C:12]([C:16]1[CH:20]=[C:19]([NH:21][C:22]([C@@H:24]2[CH2:27][CH2:26][N:25]2[C:8]([N:5]2[CH2:6][CH2:7][S:2](=[O:11])(=[O:1])[CH2:3][CH2:4]2)=[O:9])=[O:23])[O:18][N:17]=1)([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 216949071,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl chlorideHCID 67953683(S)-Azetidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide

Product 1

HCID 49847682(S)-1-(1,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl)-azetidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

1,1-Dioxo-1λ6-thiomorpholine-4-carbonyl chloride (51.4 mg; 0.26 mmol) is added to a mixture of (S)-Azetidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide; hydrochloride (69 mg; 0.265 mmol) and N,N-diisopropylethylamine (0.141 mL; 0.81 mmol) in THF (2 mL). The reaction mixture is stirred at room temperature for 2 hours. After this time, the reaction mixture is diluted with dichloromethane and washed with water. The layers are separated and the aqueous layer is extracted with dichloromethane once. The organics are combined and washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel using methanol/methylene chloride provides the title compound, m/z 385 [M+H+].

Workup

  1. washwashed with water
  2. customThe layers are separated
  3. extractionthe aqueous layer is extracted with dichloromethane once
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-80d219973ece4c0cadc9da456b7f3b87
Source dataset
uspto-grants-2013_02
Patent number
US08383615B2

Reaction notes

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