Ethanol → N-(4-(1,2,4-oxadiazol-3-yl)benzyl)-4-chloro-N-(trans-2-(hydroxymethyl)cyclopentyl)benzenesulfonamide

HRID 1011508Notes

Reaction equation

HRID 1011508 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=2)[C@@H:12]2[CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:17][OH:18])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:28]O.[CH2:30]([OH:32])C>>[O:32]1[CH:30]=[N:28][C:26]([C:23]2[CH:22]=[CH:21][C:20]([CH2:19][N:11]([C@@H:12]3[CH2:16][CH2:15][CH2:14][C@H:13]3[CH2:17][OH:18])[S:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)(=[O:10])=[O:9])=[CH:25][CH:24]=2)=[N:27]1

Participants

4

Reactant 3

HCID 702EthanolHCID 787HydroxylamineHCID 59497772HCID 59497772, compound

Product 1

HCID 59497768N-(4-(1,2,4-oxadiazol-3-yl)benzyl)-4-chloro-N-(trans-2-(hydroxymethyl)cyclopentyl)benzenesulfonamideYield 51%

Procedure

A solution of 4-chloro-N-(4-cyanobenzyl)-N-(trans-2-(hydroxymethyl)cyclopentyl)benzenesulfonamide (211 mg, 0.521 mmol) and 50% aqueous hydroxylamine (250 uL) was refluxed in ethanol (7 mL) overnight. The reaction was concentrated to dryness by rotary evaporation and co-evaporation with benzene. The dry amideoxime intermediate was then refluxed in triethylorthoformate (8 mL) under nitrogen for 5 h. After cooling to room temperature, boron trifluoride etherate (approximately 250 uL) was added and the reaction stirred overnight. The reaction was partitioned between ethyl acetate (25 mL) and brine (25 mL). The organic layer was concentrated and purified by flash chromatography on a 40 g silica gel column using a gradient of 10 to 60% ethyl acetate in hexane over 50 min to give N-(4-(1,2,4-oxadiazol-3-yl)benzyl)-4-chloro-N-(trans-2-(hydroxymethyl)cyclopentyl)benzenesulfonamide (118 mg, 51%). 1H NMR (400 MHz, CDCl3) δ ppm 8.75 (1H, s), 8.03 (2H, d), 7.70 (2H, d, J=8.56 Hz), 7.48 (2H, d, J=8.31 Hz), 7.43 (2H, d, J=8.56 Hz), 4.67 (1H, d, J=16.37 Hz), 4.106 (1H, d, J=16.37 Hz), 3.93-4.06 (1H, m), 3.33-3.61 (2H, m), 1.28-1.75 (8H, m). LC/MS R.T.=2.90 min; [M+H]+=448.16. HRMS [M+H]+ calc'd 448.1098, found 448.1087.

Workup

  1. concentrationThe reaction was concentrated to dryness by rotary evaporation and co-evaporation with benzene
  2. temperatureThe dry amideoxime intermediate was then refluxed in triethylorthoformate (8 mL) under nitrogen for 5 h
  3. additionboron trifluoride etherate (approximately 250 uL) was added
  4. customThe reaction was partitioned between ethyl acetate (25 mL) and brine (25 mL)
  5. concentrationThe organic layer was concentrated
  6. custompurified by flash chromatography on a 40 g silica gel column
  7. customover 50 min

Sources & evidence

ORD record
ord-18222efc6e224d2a96ce32f5ef434489
Source dataset
uspto-grants-2011_07
Patent number
US07977362B2

Reaction notes

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