Tetrahydrofuran → Benzyl 3-(3-(tert-butoxycarbonyl)benzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate

HRID 1751013Notes

Reaction equation

HRID 1751013 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[CH2:8][CH2:7]2)[N:5]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:4][NH:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1CCCC1.Br[CH2:44][C:45]1[CH:46]=[C:47]([CH:55]=[CH:56][CH:57]=1)[C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49]>CN(C)C=O.C(OCC)(=O)C>[C:51]([O:50][C:48]([C:47]1[CH:46]=[C:45]([CH:57]=[CH:56][CH:55]=1)[CH2:44][N:3]1[C:2](=[O:1])[C:6]2([CH2:7][CH2:8][N:9]([C:12]([O:14][CH2:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[O:13])[CH2:10][CH2:11]2)[N:5]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:4]1)=[O:49])([CH3:54])([CH3:52])[CH3:53]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 14591193tert-Butyl 3-(bromomethyl)benzoateHCID 58046755Benzyl 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate

Product 1

HCID 58046726Benzyl 3-(3-(tert-butoxycarbonyl)benzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylateYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of benzyl 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate (12.5 g, 34.21 mmol, 1 equiv), sodium bis(trimethylsilyl)amide, 1M in tetrahydrofuran (37.63 ml, 37.63 mmol, 1.1 equiv), and tert-butyl 3-(bromomethyl)benzoate (9.27 g, 34.21 mmol, 1 equiv) in N,N-dimethylformamide was stirred for 16 h at ambient temperature. Reaction was diluted with ethyl acetate and the organic layer was washed with water and brine. The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude residue was purified using the Biotage flash chromatography system (SNAP 100 g cartridge, Rf=0.6, 10%-50% ethyl acetate in hexanes) to afford benzyl 3-(3-(tert-butoxycarbonyl)benzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate (19 g, quant) as a cream solid; 1H NMR (400 MHz, DMSO-d6): δ 1.53 (s, 9H); 1.71 (d, 2H, J=13.6 Hz); 2.37-2.42 (m, 2H); 3.6 (bs, 2H); 4.01-4.03 (m, 2H); 4.61 (s, 2H); 4.64 (s, 2H); 5.14 (d, 2H, J=7.2 Hz); 6.69 (d, 2H, J=8 Hz); 6.79 (t, 2H, J=7.2 Hz); 7.16-7.2 (m, 2H); 7.32-7.39 (m, 5H); 7.49-7.56 (m, 2H); 7.81-7.85 (m, 2H); MS for C33H37N3O5 m/z 556.28 (M+H)+.

Workup

  1. customReaction
  2. washthe organic layer was washed with water and brine
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified

Sources & evidence

ORD record
ord-11dc6b5fd0fb46baba0c2c3ebf3c70d4
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

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