Hydrochloric Acid → HCID 59383088, compound

HRID 913071Notes

Reaction equation

HRID 913071 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 Mg504, 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): δ 1.46 (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): δ 14.49, 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. customThe combined organic phases were dried over Mg504
  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-e6591a008c4545adaff8fc1fcb6a5ebb
Source dataset
uspto-grants-2011_09
Patent number
US08026255B2

Reaction notes

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