Hydrochloric Acid → HCID 59383088, compound

HRID 2355542Notes

Reaction equation

HRID 2355542 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)OCC1.[CH2:11]([O:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[CH:17]=O)[CH3:12].C([BH3-])#N.[Na+].Cl>C(O)C.O.C(O)(=O)C>[CH2:11]([O:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[CH2:17][N:8]1[CH2:7][CH2:6][C:5](=[O:1])[CH2:10][CH2:9]1)[CH3:12]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 2447283-Ethoxy-4-methoxybenzaldehydeHCID 5003444Sodium cyanoborohydride

Product 1

HCID 59383088HCID 59383088, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1,4-dioxa-8-aza-spiro[4.5]decane (9.33 g, 65.16 mmol, 1.0 equiv; commercially available) and 3-ethoxy-4-methoxy-benzaldehyde (14.09 g, 78.19 mmol, 1.2 equiv; commercially available) in ethanol (50 mL) and acetic acid (5 mL) was heated to 50° C. for 1 h. Sodium cyanoborohydride (4.91 g, 78.19 mmol, 1.2 equiv), dissolved in ethanol (20 mL), was added and the reaction mixture heated to 50° C. After 2 h, a solution of 37% HCl in water (100 mL) was added and the reaction mixture heated to 100° C. for 3 h. The solvent was removed under reduced pressure and the crude reaction product extracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified with column chromatography on silica eluting with a gradient of heptane/ethyl acetate (1:3)→ethyl acetate to provide 11.23 g (59%) of the title compound. 1H NMR (300 MHz, CDCl3): δ1.46 (t, J=6.9 Hz, 3H), 2.41-2.44 (m, 4H), 2.69-2.73 (m, 4H), 3.53 (s, 2H), 3.87 (s, 3H), 4.11 (q, J=6.9 Hz, 2H), 6.80-6.86 (m, 2H), 6.94 (s, 1H). 13C NMR (75 MHz, CDCl3): δ14.49, 41.16, 52.71, 55.90, 61.00, 64.50, 111.43, 113.71, 121.04, 130.77, 148.17, 148.68, 208.71. MS (ISP): 263.9 [M+H]+.

Workup

  1. additionwas added
  2. temperaturethe reaction mixture heated to 100° C. for 3 h
  3. customThe solvent was removed under reduced pressure
  4. customthe crude reaction product
  5. extractionextracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×100 mL)
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customthe crude material purified with column chromatography on silica eluting with a gradient of heptane/ethyl acetate (1:3)→ethyl acetate

Sources & evidence

ORD record
ord-368e8a60b54b408cb0a209257f1594e3
Source dataset
uspto-grants-2010_07
Patent number
US07754744B2

Reaction notes

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