Phenacyl bromide → 2-Azido-1-phenylethanone
Reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=[O:3])[CH3:2].BrCC(C1C=CC=CC=1)=O.[N-:20]=[N+:21]=[N-:22].[Na+]>>[N:20]([CH2:2][C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3])=[N+:21]=[N-:22]Participants
Procedure
The synthesis of 2,5-substituted thiazoles is described in Scheme 9. Reaction of the desired alcohol para-methoxybenzyl alcohol (PMB-OH) with substituted 4-fluoroacetophenone 1 afforded the acetophenone intermediate 2. Acetophenone intermediate 2 was then converted to the corresponding bromo-acetophenone using Bu4NBr3 which, upon reaction with NaN3, provided the azido-acetophenone intermediate. Hydrogenation of the azido-acetophenone intermediate afforded amine 3, followed by coupling with orthogonally protected amino acid 4 gave amide 5. Removal of PMB group under hydrogenation gave phenol 6. Mitsunobu reaction of the phenol 6 with the desired alcohol followed by thiazole formation under Lawesson's reagent conditions afforded intermediate 7 in good yield. Removal of the protecting group from intermediate 7 afforded the final amino-alcohol 8.
Sources & evidence
- ORD record
- ord-37739129b4664daa8d20414e5f28b01b
- Source dataset
- uspto-grants-2010_07
- Patent number
- US07759370B2
Reaction notes
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