1-Phenylpiperazine → tert-butyl (6S,7S)-6-(4-phenylpiperazine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxylate

HRID 2240508Notes

Reaction equation

[C:1]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:13]([O:17][C:18]([C@H:20]1[CH2:27][C:24]2([CH2:26][CH2:25]2)[CH2:23][NH:22][C@@H:21]1[C:28](O)=[O:29])=[O:19])([CH3:16])([CH3:15])[CH3:14].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.C([O-])(O)=O.[Na+]>[C:1]1([N:7]2[CH2:12][CH2:11][N:10]([C:28]([C@@H:21]3[C@@H:20]([C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])[CH2:27][C:24]4([CH2:25][CH2:26]4)[CH2:23][NH:22]3)=[O:29])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

Conditions

Temperature: 0 °C

Procedure

1-Phenylpiperazine (124 mg, 0.76 mmol) was added to a mixture of (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2.5]octane-6-carboxylic acid (180 mg, 0.70 mmol) and BOP (320 mg, 0.75 mmol) in DMF (4 mL) at 0° C. The mixture was stirred at 0° C. for 10 min, then N-methylmorphol (300 μL) was added. The resulting mixture was stirred at RT for overnight, diluted with 5% NaHCO3 and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with saturated brine and dried over Na2SO4. The solution was filtered and concentrated to afford 248.4 mg of the tert-butyl(6S,7S)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxylate.

Workup

additionN-methylmorphol (300 μL) was added
stirringThe resulting mixture was stirred at RT for overnight
extractionextracted with ethyl acetate (3×10 mL)
washThe combined organic layers were washed with saturated brine
dry with materialdried over Na2SO4
filtrationThe solution was filtered
concentrationconcentrated

Sources & evidence

ORD record: ord-e65de24f370141a3800fc59c07cd4af1
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723349B2

Reaction notes

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