N-(1-bicyclo[1.1.1]pentanyl)acetamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The C—H activation/oxidation (Scheme 4) of commercially available bicyclo[1.1.1]pentan-1-amine by an appropriate oxidizing reagent or condition (for example, H2SO4 (conc.)/HNO3 (conc. or 50%); H2SO4 (conc.)/NH4NO3; perfluoro-cis-2-n-butyl-3-n-propyloxaziridine; CBr4/H2O/Mo(CO)6; [(Me3tacn)RuCl3], CAN, AgClO4, t-BuOH/H2O; RuCl3-xH2O, KBrO3, H2O, pyridine, CH3CN; dimethyldioxirane (DMD) or methyl(trifluoromethyl)dioxirane (TFDO), with or without HBF4; CrO3, H5IO6; KMnO4, KOH; and the like) can give 3-aminobicyclo[1.1.1]pentan-1-ol. The amino alcohol intermediate can then be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride to give 3-acetamidobicyclo[1.1.1]pentan-1-yl acetate (3). Selective hydrolysis of the ester group with hydroxide ion gives N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1). Alternatively, starting with N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4), C—H activation/oxidation with an appropriate oxidizing reagent or conditions (for example, see listed above, and H2SO4 (conc.), (CF3CO)2O; NaNO2, TFA, O2; CrO3, CH3CO2H, (H3CO)2O; RuCl3 (cat.), TFA, DCM, peracetic acid; DDQ, TfOH; and the like) can give N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The commercially available bicyclo[1.1.1]pentan-1-amine can be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride in the presence of base (for example, K2CO3, Na2CO3, NaHCO3, TEA, pyridine, and the like) to give N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4) (Scheme 3).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The C—H activation/oxidation (Scheme 3) of commercially available bicyclo[1.1.1]pentan-1-amine by an appropriate oxidizing reagent or condition (for example, H2SO4 (conc.)/HNO3 (conc. or 50%); H2SO4 (conc.)/NH4NO3; perfluoro-cis-2-n-butyl-3-n-propyloxaziridine; CBr4/H2O/Mo(CO)6; [(Me3tacn)RuCl3], CAN, AgClO4, t-BuOH/H2O; RuCl3-xH2O, KBrO3, H2O, pyridine, CH3CN; dimethyldioxirane (DMD) or methyl(trifluoromethyl)dioxirane (TFDO), with or without HBF4; CrO3, H5IO6; KMnO4, KOH; and the like) can give 3-aminobicyclo[1.1.1]pentan-1-ol. The amino alcohol intermediate can then be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride to give 3-acetamidobicyclo[1.1.1]pentan-1-yl acetate (3). Selective hydrolysis of the ester group with hydroxide ion gives N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1). Alternatively, starting with N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4), C—H activation/oxidation with an appropriate oxidizing reagent or conditions (for example, see listed above, and H2SO4 (conc.), (CF3CO)2O; NaNO2, TFA, O2; CrO3, CH3CO2H, (H3CO)2O; RuCl3 (cat.), TFA, DCM, peracetic acid; DDQ, TfOH; and the like) can give N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The commercially available bicyclo[1.1.1]pentan-1-amine can be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride in the presence of base (for example, K2CO3, Na2CO3, NaHCO3, TEA, pyridine, and the like) to give N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4) (Scheme 2).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The C—H activation/oxidation (Scheme 4) of commercially available bicyclo[1.1.1]pentan-1-amine by an appropriate oxidizing reagent or condition (for example, H2SO4 (conc.)/HNO3 (conc. or 50%); H2SO4 (conc.)/NH4NO3; perfluoro-cis-2-n-butyl-3-n-propyloxaziridine; CBr4/H2O/Mo(CO)6; [(Me3tacn)RuCl3], CAN, AgClO4, t-BuOH/H2O; RuCl3-xH2O, KBrO3, H2O, pyridine, CH3CN; dimethyldioxirane (DMD) or methyl(trifluoromethyl)dioxirane (TFDO), with or without HBF4; CrO3, H5IO6; KMnO4, KOH; and the like) can give 3-aminobicyclo[1.1.1]pentan-1-ol. The amino alcohol intermediate can then be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride to give 3-acetamidobicyclo[1.1.1]pentan-1-yl acetate (3). Selective hydrolysis of the ester group with hydroxide ion gives N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1). Alternatively, starting with N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4), C—H activation/oxidation with an appropriate oxidizing reagent or conditions (for example, see listed above, and H2SO4 (conc.), (CF3CO)2O; NaNO2, TFA, O2; CrO3, CH3CO2H, (H3CO)2O; RuCl3 (cat.), TFA, DCM, peracetic acid; DDQ, TfOH; and the like) can give N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The commercially available bicyclo[1.1.1]pentan-1-amine can be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride in the presence of base (for example, K2CO3, Na2CO3, NaHCO3, TEA, pyridine, and the like) to give N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4) (Scheme 3).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The C—H activation/oxidation (Scheme 3) of commercially available bicyclo[1.1.1]pentan-1-amine by an appropriate oxidizing reagent or condition (for example, H2SO4 (conc.)/HNO3 (conc. or 50%); H2SO4 (conc.)/NH4NO3; perfluoro-cis-2-n-butyl-3-n-propyloxaziridine; CBr4/H2O/Mo(CO)6; [(Me3tacn)RuCl3], CAN, AgClO4, t-BuOH/H2O; RuCl3-xH2O, KBrO3, H2O, pyridine, CH3CN; dimethyldioxirane (DMD) or methyl(trifluoromethyl)dioxirane (TFDO), with or without HBF4; CrO3, H5IO6; KMnO4, KOH; and the like) can give 3-aminobicyclo[1.1.1]pentan-1-ol. The amino alcohol intermediate can then be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride to give 3-acetamidobicyclo[1.1.1]pentan-1-yl acetate (3). Selective hydrolysis of the ester group with hydroxide ion gives N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1). Alternatively, starting with N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4), C—H activation/oxidation with an appropriate oxidizing reagent or conditions (for example, see listed above, and H2SO4 (conc.), (CF3CO)2O; NaNO2, TFA, O2; CrO3, CH3CO2H, (H3CO)2O; RuCl3 (cat.), TFA, DCM, peracetic acid; DDQ, TfOH; and the like) can give N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The commercially available bicyclo[1.1.1]pentan-1-amine can be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride in the presence of base (for example, K2CO3, Na2CO3, NaHCO3, TEA, pyridine, and the like) to give N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4) (Scheme 2).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The C—H activation/oxidation (Scheme 4) of commercially available bicyclo[1.1.1]pentan-1-amine by an appropriate oxidizing reagent or condition (for example, H2SO4 (conc.)/HNO3 (conc. or 50%); H2SO4 (conc.)/NH4NO3; perfluoro-cis-2-n-butyl-3-n-propyloxaziridine; CBr4/H2O/Mo(CO)6; [(Me3tacn)RuCl3], CAN, AgClO4, t-BuOH/H2O; RuCl3-xH2O, KBrO3, H2O, pyridine, CH3CN; dimethyldioxirane (DMD) or methyl(trifluoromethyl)dioxirane (TFDO), with or without HBF4; CrO3, H5IO6; KMnO4, KOH; and the like) can give 3-aminobicyclo[1.1.1]pentan-1-ol. The amino alcohol intermediate can then be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride to give 3-acetamidobicyclo[1.1.1]pentan-1-yl acetate (3). Selective hydrolysis of the ester group with hydroxide ion gives N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1). Alternatively, starting with N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4), C—H activation/oxidation with an appropriate oxidizing reagent or conditions (for example, see listed above, and H2SO4 (conc.), (CF3CO)2O; NaNO2, TFA, O2; CrO3, CH3CO2H, (H3CO)2O; RuCl3 (cat.), TFA, DCM, peracetic acid; DDQ, TfOH; and the like) can give N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The commercially available bicyclo[1.1.1]pentan-1-amine can be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride in the presence of base (for example, K2CO3, Na2CO3, NaHCO3, TEA, pyridine, and the like) to give N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4) (Scheme 3).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The C—H activation/oxidation (Scheme 3) of commercially available bicyclo[1.1.1]pentan-1-amine by an appropriate oxidizing reagent or condition (for example, H2SO4 (conc.)/HNO3 (conc. or 50%); H2SO4 (conc.)/NH4NO3; perfluoro-cis-2-n-butyl-3-n-propyloxaziridine; CBr4/H2O/Mo(CO)6; [(Me3tacn)RuCl3], CAN, AgClO4, t-BuOH/H2O; RuCl3-xH2O, KBrO3, H2O, pyridine, CH3CN; dimethyldioxirane (DMD) or methyl(trifluoromethyl)dioxirane (TFDO), with or without HBF4; CrO3, H5IO6; KMnO4, KOH; and the like) can give 3-aminobicyclo[1.1.1]pentan-1-ol. The amino alcohol intermediate can then be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride to give 3-acetamidobicyclo[1.1.1]pentan-1-yl acetate (3). Selective hydrolysis of the ester group with hydroxide ion gives N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1). Alternatively, starting with N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4), C—H activation/oxidation with an appropriate oxidizing reagent or conditions (for example, see listed above, and H2SO4 (conc.), (CF3CO)2O; NaNO2, TFA, O2; CrO3, CH3CO2H, (H3CO)2O; RuCl3 (cat.), TFA, DCM, peracetic acid; DDQ, TfOH; and the like) can give N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The commercially available bicyclo[1.1.1]pentan-1-amine can be coupled with an appropriate carboxylic acid or acid chloride, such as acetyl chloride in the presence of base (for example, K2CO3, Na2CO3, NaHCO3, TEA, pyridine, and the like) to give N-(bicyclo[1.1.1]pentan-1-yl)acetamide (4) (Scheme 2).