Triethylamine → (S)-8-(2-chloro-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1848537Notes

Reaction equation

HRID 1848537 reaction equation
O[C@H:2]([C:22]1[CH:31]=[CH:30][C:25]2[C:26](=[O:29])[O:27][CH2:28][C:24]=2[C:23]=1[CH3:32])[CH2:3][N:4]1[CH2:21][CH2:20][C:7]2([C:11](=[O:12])[N:10]([C:13]3[CH2:14][O:15][C:16](=[O:19])[C:17]=3[CH3:18])[CH2:9][CH2:8]2)[CH2:6][CH2:5]1.CS([Cl:37])(=O)=O.C(N(CC)CC)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:37][C@@H:2]([C:22]1[C:23]([CH3:32])=[C:24]2[C:25](=[CH:30][CH:31]=1)[C:26](=[O:29])[O:27][CH2:28]2)[CH2:3][N:4]1[CH2:21][CH2:20][C:7]2([C:11](=[O:12])[N:10]([C:13]3[CH2:14][O:15][C:16](=[O:19])[C:17]=3[CH3:18])[CH2:9][CH2:8]2)[CH2:6][CH2:5]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 729500748-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Product 1

HCID 86709526(S)-8-(2-chloro-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one (Example 7) (1.1 g, 2.5 mmol) and methanesulfonyl chloride (0.584 mL, 7.49 mmol) in DCM (30 mL) was added triethylamine (1.22 mL, 8.74 mmol) and N,N-dimethylpyridin-4-amine (0.031 g, 0.250 mmol) at −10 to −15° C. (ice-NaCl). The mixture was stirred at the same temperature for 20 min, quenched with NH4Cl aqueous. The organic layer was separated, and the aqueous was extracted with DCM (30 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to give product was used in the next step without further purification. LCMS: 459.05 (M+1).

Workup

  1. customquenched with NH4Cl aqueous
  2. customThe organic layer was separated
  3. extractionthe aqueous was extracted with DCM (30 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customto give product
  7. customwas used in the next step without further purification

Sources & evidence

ORD record
ord-1c92bd41603241989dddb2af39474730
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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