Acetic Acid → HCID 25139487, compound

HRID 1669159Notes

Reaction equation

HRID 1669159 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[O-:7][N+:8]1[C:13]2[CH:14]=[C:15]3[CH2:20][CH2:19][O:18][C:16]3=[CH:17][C:12]=2[N:11]=[C:10]([CH2:21][CH2:22][CH:23]=O)[N:9]=1.[BH3-]C#N.[Na+].CC(O)=O>CO.CN(C=O)C>[N:1]1([CH2:23][CH2:22][CH2:21][C:10]2[N:9]=[N+:8]([O-:7])[C:13]3[CH:14]=[C:15]4[CH2:20][CH2:19][O:18][C:16]4=[CH:17][C:12]=3[N:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5003444Sodium cyanoborohydrideHCID 25140183HCID 25140183, compound

Product 1

HCID 25139487HCID 25139487, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Morpholine (0.22 mL, 2.52 mmol) was added to a solution of aldehyde 214 (220 mg, 0.90 mmol) in MeOH (10 mL) and DMF (10 ml), and the solution stirred for 30 min. NaCNBH3 (176 mg, 2.80 mmol) was added, followed by HOAc (0.12 mL) and the mixture stirred at 20° C. for 30 min. The solvent was evaporated and the residue partitioned between DCM (40 mL) and water (40 mL). The aqueous phase was extracted with DCM (2×40 mL), the combined organic phase was dried and the solvent evaporated. The residue was purified by chromatography, eluting with 10% MeOH/EtOAc, to give 1-oxide 215 (210 mg, 74%) as a pale brown solid, mp 96-99° C.; 1H NMR δ 8.27 (t, J=1.6 Hz, 1H, H-9), 7.11 (s, 1H, H-5), 4.80 (t, J=8.4 Hz, 2H, H-8), 3.59 (t, J=4.6 Hz, 4H, 2×CH2O), 3.43 (dt, J=8.4, 1.6 Hz, 2H, H-7), 2.97-3.01 (m, 2H, CH2), 2.44-2.48 (m, 2H, CH2), 2.41 (t, J=4.5 Hz, 4H, 2×CH2N), 2.03-2.11 (m, 2H, CH2); 13C NMR δ 167.1, 166.4, 150.5, 134.8, 128.9, 116.2, 103.9, 73.0, 67.0 (2), 58.3, 53.5 (2), 53.4, 27.0, 24.9. Anal. calcd for C16H20N4O3: C, 60.8; H, 6.4; N, 17.7. Found: C, 60.7; H, 6.5; N, 17.7%.

Workup

  1. stirringthe mixture stirred at 20° C. for 30 min
  2. customThe solvent was evaporated
  3. customthe residue partitioned between DCM (40 mL) and water (40 mL)
  4. extractionThe aqueous phase was extracted with DCM (2×40 mL)
  5. customthe combined organic phase was dried
  6. customthe solvent evaporated
  7. customThe residue was purified by chromatography
  8. washeluting with 10% MeOH/EtOAc

Sources & evidence

ORD record
ord-6b9438628d474055bfcfe63108f037ca
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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