Hydroxylamine → HCID 42599459, compound

HRID 1362571Notes

Reaction equation

HRID 1362571 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([NH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=O)=[O:12].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:34][OH:35].Cl.NO>O1CCCC1.CN(C)C=O.C(N(CC)CC)C>[OH:35][NH:34][C:19]([CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][NH:13][C:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)=[O:12])=[O:21]

Participants

8

Reactant 4

HCID 787Hydroxylamine2×HCID 682631,1'-CarbonyldiimidazoleHCID 443297Hydroxyamine hydrochlorideHCID 14196781HCID 14196781, compound

Product 1

HCID 42599459HCID 42599459, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

(Method J5C) A solution of 6-[(naphthalene-2-carbonyl)amino]hexanoic acid (4/53) (0.618 g, 2.17 mmol) in dry tetrahydrofuran (6 ml) was cooled in ice bath under argon atmosphere and 1,1′-carbonyldiimidazole (0.422 g, 2.6 mmol) was added. The mixture was stirred for 30 min. and a solution of hydroxylamine (4.35 mmol) in dry dimethylformamide (3 ml) [the solution of hydroxylamine was made from hydroxylamine hydrochloride (0.302 g, 4.35 mmol) and triethylamine (0.61 ml) in dimethylformamide (3 ml) and filtered] was added. After stirring overnight the reaction mixture was diluted with saturated NaH2PO4 (30 ml) and extracted with ethyl acetate (3×30 ml). The organic phase was evaporated under reduced pressure by adding several times of benzene to remove traces of water. The crude product was crystallized successively from ethyl acetate and acetonitrile to give of the title compound (0.260 g, 40%), m.p. 96-98° C. 1H NMR (DMSO-d6, HMDSO), δ: 1.21-1.45 (2H, m); 1.46-1.73 (4H, m); 1.89-2.05 (2H, m); 3.25-3.37 (2H, m); 7.65-7.81 (2H, m); 7.86-8.04 (4H, m); 8.42 (1H, s); 8.56-8.72 (2H, m); 10.32 (1H, s). HPLC analysis on Symmetry C8 column: impurities <1% (column size 3.9×150 mm; mobile phase 40% acetonitrile+60% 0.1% H3PO4; detector UV 220 nm; sample concentration 0.145 mg/ml). Anal. Calcd, %: C, 67.98; H, 6.71; N, 9.33; Found, %: C, 68.29; H, 6.97; N, 8.99.

Workup

  1. filtrationfiltered]
  2. additionwas added
  3. stirringAfter stirring overnight the reaction mixture
  4. additionwas diluted with saturated NaH2PO4 (30 ml)
  5. extractionextracted with ethyl acetate (3×30 ml)
  6. customThe organic phase was evaporated under reduced pressure
  7. additionby adding several times of benzene
  8. customto remove traces of water
  9. customThe crude product was crystallized successively from ethyl acetate and acetonitrile

Sources & evidence

ORD record
ord-72a11826aa2542b2856ea176d247ad49
Source dataset
uspto-grants-2011_02
Patent number
US07880020B2

Reaction notes

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