Acetic Acid → 8-(3-Ethoxy-4-methyl-benzyl)-1,3,8-triaza-spiro[4.5]decane-2,4-dione

HRID 913306Notes

Reaction equation

[NH:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[C:4](=[O:11])[NH:3][C:2]1=[O:12].C(O)(=O)C.C(N(C(C)C)C(C)C)C.[CH2:26]([O:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[CH3:37])[CH:32]=O)[CH3:27].C([BH3-])#N.[Na+]>C(O)C>[CH2:26]([O:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[CH3:37])[CH2:32][N:8]1[CH2:9][CH2:10][C:5]2([NH:1][C:2](=[O:12])[NH:3][C:4]2=[O:11])[CH2:6][CH2:7]1)[CH3:27]

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 1,3,8-triaza-spiro[4.5]decane-2,4-dione (25.4 mg, 0.15 mmol, 1.0 equiv; intermediate A1) in ethanol (1 mL), acetic acid (72.1 mg, 1.2 mmol, 8.0 equiv) and N-ethyl diisopropylamine (77.6 mg, 0.6 mmol, 4.0 equiv) was added 3-ethoxy-4-methyl-benzaldehyde (29.6 mg, 0.18 mmol, 1.2 equiv; intermediate B10, vide infra) and the mixture stirred at 55° C. After 1 h, sodium cyanoborohydride (47.1 mg, 0.75 mmol, 5.0 equiv), dissolved in ethanol (0.5 mL), was added and the mixture stirred at 55° C. over night. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 8.6 mg (17%) of the title compound. MS (ISP): 338.2 [M+H]+.

Workup

additionwas added
stirringthe mixture stirred at 55° C. over night
customRemoval of the solvent
customunder reduced pressure and purification by preparative HPLC on reversed phase
washeluting with a gradient of acetonitrile/water

Sources & evidence

ORD record: ord-33d0e04fd4f442bf8a2e1974f40931b3
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026365B2

Reaction notes

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