Hydrochloric Acid → 8-{4-[(Hydroxyamino)methyl]phenyl]-1,4-dioxa-8-azaspiro[4.5]decane

HRID 1061225Notes

Reaction equation

HRID 1061225 reaction equation
Cl.[O:2]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]3[CH:20]=[CH:19][C:15]([CH:16]=[N:17][OH:18])=[CH:14][CH:13]=3)[CH2:8][CH2:7]2)[O:5][CH2:4][CH2:3]1.C([BH3-])#N.[Na+].[OH-].[Na+]>CN(C1C=CC(N=NC2C=CC(S(O)(=O)=O)=CC=2)=CC=1)C.O.CO>[OH:18][NH:17][CH2:16][C:15]1[CH:19]=[CH:20][C:12]([N:9]2[CH2:8][CH2:7][C:6]3([O:5][CH2:4][CH2:3][O:2]3)[CH2:11][CH2:10]2)=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 73178202HCID 73178202, compound

Product 1

HCID 129659608-{4-[(Hydroxyamino)methyl]phenyl]-1,4-dioxa-8-azaspiro[4.5]decaneYield 78.5%

Reagents, catalysts & solvents 3

HCID 11037Benzenesulfonic acid, 4-(2-(4-(dimethylamino)phenyl)diazenyl)-CatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Hydrochloric acid (4N, in dioxane) was added dropwise into a mixture of 4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)benzaldehyde oxime (5.3 g, 20.24 mmol) (which was obtained in Example 51), sodium cyanoborohydride (6.3 g, 101.2 mmol), methyl alcohol(200 mL), and methyl orange (10 mg), until an acidic solution (pH about 4) was achieved. The mixture was then stirred for 1 hour, poured into water, neutralized with NaOH (2N) and extracted with ethyl acetate. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography (hexanes/ethyl acetate/methyl alcohol 10/5/1) gave a white solid (4.2 g, 78% yield); mp 107-109° C,; 1H NMR (400 MHz, DMSO-d6) δ 1.64 (m, 4H), 3.20 (m, 4H), 3.74 (s, 2H), 3.90 (s, 4H), 5.84 (brs, 1H), 6.86 (m, 2H), 7.14 (m, 2H), 7.19 (brs, 1H); MS (ES) m/z: 265 (MH+).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic extracts were dried over MgSO4
  3. customEvaporation and purification by flash chromatography (hexanes/ethyl acetate/methyl alcohol 10/5/1)

Sources & evidence

ORD record
ord-7d031e0279494355b6ebb5bf63a96752
Source dataset
uspto-grants-2003_02
Patent number
US06525202B2

Reaction notes

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