Chlorine → HCID 68671999, compound

HRID 2038576Notes

Reaction equation

HRID 2038576 reaction equation
ClCl.[Cl:3][C:4]1[CH:5]=[C:6]([N:10]2[C:32](=[O:33])[CH2:31][C@@:12]3([CH2:16][N:15](C(OC(C)(C)C)=O)[C@H:14]([C:24]([O:26][C:27](C)(C)C)=[O:25])[CH2:13]3)[CH2:11]2)[CH:7]=[CH:8][CH:9]=1>C(#N)C.O>[Cl:3][C:4]1[CH:5]=[C:6]([N:10]2[C:32](=[O:33])[CH2:31][C@@:12]3([CH2:16][NH:15][C@H:14]([C:24]([O:26][CH3:27])=[O:25])[CH2:13]3)[CH2:11]2)[CH:7]=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 24526ChlorineHCID 59547306HCID 59547306, compound

Product 1

HCID 68671999HCID 68671999, compoundYield 105.9%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

The arylated lactam (3S,5S)-di-tert-butyl-7-(3-chlorophenyl)-8-oxo-2,7-diazaspiro[4.4]nonane-2,3-dicarboxylate (A7a) (45.7 mg, 101 μmol) was taken up in 1M HCl in ethyl acetate (1.0 ml, 10 eq). The reaction was aged at room temperature overnight. The reaction was purged by bubbling N2 gas through it, until dry. The product was then taken up in a saturated solution of hydrochloric acid in methanol (2 ml), and aged at room temperature overnight. The reaction was blown dry with nitrogen gas and dried in-vacuo to give (3S,5R) methyl-7-(3-chlorophenyl)-8-oxo-2,7-diazaspiro[4.4]nonane-3-carboxylate (B7a) (35.2 mg, 102 μmol). LCMS for C15H17N2O3Cl 308.09 [M], found ES+ 309.2 [M+H]+ and 311.1 [M+H]+ (for the chlorine isotope) at 2.0 minutes retention time, using 5-45% acetonitrile/water (with 0.1% formic acid buffer) gradient over 7 minutes. The minor diastereomer (3S,5R)-di-tert-butyl 7-(3-chlorophenyl)-8-oxo-2,7-diazaspiro[4.4]nonane-2,3-dicarboxylate (A7b) (15.2 mg, 34 μmol) was treated similarly to give (3S,5S)-methyl 7-(3-chlorophenyl)-8-oxo-2,7-diazaspiro[4.4]nonane-3-carboxylate (B7b) (12.4 mg, 36 μmol). LCMS for C15H17N2O3Cl 308.09 [M], found ES+ 309.2 [M+H]+ and 311.1 [M+H]+ (for the chlorine isotope) at 2.2 minutes retention time, using 5-45% acetonitrile/water (with 0.1% formic acid buffer) gradient over 7 minutes.

Workup

  1. customat 2.0 minutes
  2. customover 7 minutes

Sources & evidence

ORD record
ord-1b35ce5abaf34836bf07f0053619718e
Source dataset
uspto-grants-2013_11
Patent number
US08575208B2

Reaction notes

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