Acetyl chloride → 3-Acetamidobicyclo[1.1.1]pentan-1-yl acetate
Reaction equation
[C:1]([O:4][C:5]12[CH2:9][C:7]([NH2:10])([CH2:8]1)[CH2:6]2)(=[O:3])[CH3:2].[C:11](Cl)(=[O:13])[CH3:12]>>[C:1]([O:4][C:5]12[CH2:9][C:7]([NH:10][C:11](=[O:13])[CH3:12])([CH2:8]1)[CH2:6]2)(=[O:3])[CH3:2]Participants
Procedure
The commercially available 3-aminobicyclo[1.1.1]pentane-1-carboxylic acid can be converted to the methyl ketone intermediate by treatment with either methyl lithium or methylmagnesium bromide (Scheme 1). Baeyer-Villagar type oxidation with mCPBA or other peroxycarboxylic acids can give 3-aminobicyclo[1.1.1]pentan-1-yl acetate. The amine 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 the commercially available 3-hydroxybicyclo[1.1.1]pentane-1-carboxylic acid and carrying out a Curtius reaction or modified Curtius reaction using diphenylphosphoryl azide gives the amino alcohol intermediate, which can then be treated with acetyl chloride (1 eq) in the presence of base (for example, K2CO3, Na2CO3, TEA, and the like) to give N-(3-hydroxybicyclo[1.1.1]pentan-1-yl)acetamide (1) or with acetyl chloride (>2 eq) in the presence of base (for example, K2CO3, Na2CO3, TEA, and the like) to give 3-acetamidobicyclo[1.1.1]pentan-1-yl acetate (3).
Sources & evidence
- ORD record
- ord-5b20e2777c2e4feaa44930d83691cd67
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09447025B2
Reaction notes
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