(1R,2R)-2-Aminocyclohexanol → N-(4-(Oxetan-3-YL)phenyl)acetamide

HRID 2040703

Reaction equation

HRID 2040703 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].N[C@@H]1CC[CH2:18][CH2:17][C@H:16]1[OH:21].C[Si](C)(C)N[Si](C)(C)C.[Na].IC1COC1>C(O)(C)C.CCO.[Ni](I)I>[O:21]1[CH2:16][CH:17]([C:8]2[CH:9]=[CH:10][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:6][CH:7]=2)[CH2:18]1

Participants

8

Reactant 4

HCID 735777(1R,2R)-2-AminocyclohexanolHCID 27346574-Acetamidophenylboronic acidHCID 133566863-IodooxetaneHCID 45051731Sodium hexamethyidisilazane

Product 1

HCID 67776166N-(4-(Oxetan-3-YL)phenyl)acetamideYield 950.8%

Reagents, catalysts & solvents 3

HCID 26038Nickel(II) iodideCatalystHCID 702EthanolSolventHCID 3776IsopropanolSolvent2×

Conditions

Temperature
80 °C

Procedure

(4-Acetamidophenyl)boronic acid (670 mg, 3.7 mmol), Nickel (II) iodide (35 mg, 0.11 mmol), trans-2-aminocyclohexanol (17 mg, 0.11 mmol), and Sodium hexamethyldisilazane (690 mg, 3.7 mmol) were weighed into a microwave reaction vial. A septum was placed over the top, nitrogen was purged and Isopropyl alcohol (5.7 ml, 75 mmol) was added. The vial was purged with nitrogen for 10 minutes and 3-iodooxetane (344 mg, 1.87 mmol) was added in 0.75 ml isopropyl alcohol. The septum was replaced with a microwave vial cap and the mixture was heated in a microwave reactor (microwave conditions: CEM Discovery Explorer microwave reactor; Ramp time: 10 min; 80° C. for 30 min; power: 300 W). The crude reaction mixture was diluted with 8 ml EtOH and the suspension was filtered through a pad of Solka floc®. The pad was washed with 35 ml EtOH and the filtrate was concentrated. The crude material was purified by flash chromatography (SiO2, eluting with 40-60% EtOAc/CH2Cl2) to give the desired product as an oil (200 mg).

Workup

  1. customwas purged
  2. customThe vial was purged with nitrogen for 10 minutes
  3. customvial cap
  4. customThe crude reaction mixture
  5. filtrationthe suspension was filtered through a pad of Solka floc®
  6. washThe pad was washed with 35 ml EtOH
  7. concentrationthe filtrate was concentrated
  8. customThe crude material was purified by flash chromatography (SiO2, eluting with 40-60% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-a4e4a7951d57439c920b40d2b37377b9
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Linked notes

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