Dimethylformamide → HCID 10591040, compound

HRID 1377913Notes

Reaction equation

HRID 1377913 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:22]=[CH:21][C:12]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18](O)=[O:19])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)#[N:2].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[Si]([O:41][NH2:42])(C(C)(C)C)(C)C.C(N(CC)CC)C>C1COCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:22]=[CH:21][C:12]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([NH:42][OH:41])=[O:19])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 10402234HCID 10402234, compound

Product 1

HCID 10591040HCID 10591040, compoundYield 45.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution in THF (13 mL) of 5-(4-(4-cyanophenyl)phenoxy)pentanoic acid (0.50 g, 1.7 mmol), prepared as in step 1, was added DMF (10 μL, 0.13 mmol), and oxalyl chloride (0.16 mL, 1.9 mmol) and the reaction mixture was stirred for 2 hours. A solution in THF (2 mL) of O-tert-butyldimethylsilylhydroxylamine (0.30 g, 2.0 mmol) and triethylamine (0.25 mL, 1.8 mmol) was added dropwise via syringe and the reaction mixture was stirred for 3.5 hours. The reaction mixture was quenched with methanol and concentrated in vacuo. The residue was partitioned between aqueous 1M NaOH and ethyl ether, and the aqueous phase was extracted with ethyl ether. The aqueous phase was taken to pH 2 with concentrated HCl and extracted three times with dichloromethane. The combined dichloromethane extracts were dried over Na2SO4, filtered, and concentrated in vacuo to give a white solid. Recrystallization from ethyl acetate gave 5-[4-(4-cyanophenyl)phenoxy]pentanohydroxamic acid (0.24 g) as a white solid. mp 141.8°-142.6° C. 1H NMR (DMSO-d6) δ 1.59-1.84 (c, 4H), 2.03 (t, 2H, J=7.5 Hz), 4.03 (t, 2H, J=6 Hz), 7.06 (d, 2H, J=9 Hz), 7.69 (s, 1H), 7.72 (s, 1H), 7.81-7.92 (c, 4H), 8.71 (s, 1H), 10.39 (s, 1H). IR (KBr) 3200, 3030, 3010, 2860, 2240, 1630, 1600, 1540, 1520, 1490, 1470, 1460, 1390, 1290, 1250, 1180, 1110, 980, 850, 820, 630, 580, 530 cm-1. MS (DCI/NH3) 294 (M-16), 311 (M+H)+, 328 (M+NH4)+. Anal. Calcd for C18H18N2O3 : C, 69.66; H, 5.85; N, 9.03. Found: C, 69.54; H, 5.73; N, 8.99.

Workup

  1. stirringthe reaction mixture was stirred for 3.5 hours
  2. customThe reaction mixture was quenched with methanol
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between aqueous 1M NaOH and ethyl ether
  5. extractionthe aqueous phase was extracted with ethyl ether
  6. extractionextracted three times with dichloromethane
  7. dry with materialThe combined dichloromethane extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a white solid
  11. customRecrystallization from ethyl acetate

Sources & evidence

ORD record
ord-86b83bcd7ca24891a16fee3fbf3d2ab2
Source dataset
uspto-grants-1997_09
Patent number
US05665777

Reaction notes

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