Diisopropylethylamine → 6-(2-Methoxycarbonylamino-3-methyl-butyryl)-5-oxa-6-aza-spiro[3.4]octane-7-carboxylic acid ethyl ester

HRID 79979Notes

Reaction equation

HRID 79979 reaction equation
[CH3:1][O:2][C:3]([NH:5][CH:6]([CH:10]([CH3:12])[CH3:11])[C:7]([OH:9])=O)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:37]([O:39][C:40]([CH:42]1[CH2:49][C:45]2([CH2:48][CH2:47][CH2:46]2)[O:44][NH:43]1)=[O:41])[CH3:38].C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH2:37]([O:39][C:40]([CH:42]1[CH2:49][C:45]2([CH2:46][CH2:47][CH2:48]2)[O:44][N:43]1[C:7](=[O:9])[CH:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[CH:10]([CH3:12])[CH3:11])=[O:41])[CH3:38]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 138211012-((Methoxycarbonyl)amino)-3-methylbutanoic acidHCID 59611538Ethyl 5-oxa-6-azaspiro[3.4]octane-7-carboxylate

Product 1

HCID 666206496-(2-Methoxycarbonylamino-3-methyl-butyryl)-5-oxa-6-aza-spiro[3.4]octane-7-carboxylic acid ethyl esterYield 72.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-methoxycarbonylamino-3-methyl-butyric acid (1.11 g, 6.33 mmol) and HATU (2.41 g, 6.34 mmol) in dimethylformamide (13 mL) was added a solution of 5-oxa-6-aza-spiro[3.4]octane-7-carboxylic acid ethyl ester (980 mg, 5.3 mmol) in dimethylformamide (13 mL). To the resulting reaction mixture was added diisopropylethylamine (1.85 mL, 10.6 mmol) and the reaction was heated to 60° C. for 16 hours. The reaction was diluted with ethyl acetate, washed with water and brine, dried (MgSO4) and concentrated. The resulting residue was purified by flash chromatography to give 6-(2-methoxycarbonylamino-3-methyl-butyryl)-5-oxa-6-aza-spiro[3.4]octane-7-carboxylic acid ethyl ester (1.31 g, 72%). LCMS-ESI+: calculated for C16H26N2O6: 342.18; observed [M+1]+: 342.90.

Workup

  1. customTo the resulting reaction mixture
  2. washwashed with water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-cf4deb46546a49aab00dce4cbee52581
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Reaction notes

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