2-Amino-2-methyl-1-propanol → HCID 46837646, compound
Reaction equation
[NH2:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].FC(F)(F)S(O[C@H:13]([CH3:18])[C:14](OC)=[O:15])(=O)=O>>[CH3:18][C@H:13]1[C:14](=[O:15])[O:4][CH2:3][C:2]([CH3:6])([CH3:5])[NH:1]1Participants
Procedure
In some embodiments, various compounds of the present invention (e.g., 4h-m and 4o) were prepared by a novel convergent synthetic approach for the preparation of 2-substituted morpholinols as outlined in Scheme 3. This new approach utilized a nucleophilic addition of Grignard reagents to (3S)-3,5,5-trimethylmorpholin-2-one (15). Treatment of methyl (R)-(+)-lactate (13) with trifluoromethanesulfonic anhydride and 2,6-lutidine at 0° C., gave methyl (2R)-2-{[(trifluoromethyl)sulfonyl]oxy}propionate (14) in 77% yield. The alkylation of 2-amino-2-methyl-1-propanol with triflate 14 at −40° C. for 2 h and overnight at room temperature, and subsequent cyclization afforded 15 in 63% yield. To test the approach, reaction of lactone 15 with 3-chlorophenylmagnesium bromide resulted in the formation of (2S,3S)-trimethyl-2-(3′-chlorophenyl)morpholin-2-ol [(2S,3S)-4-a] in 32% yield (98% ee), 16% overall from (R)-(+)-lactate (13). The addition of the appropriate arylmagnesium bromide to 15 provided the desired compounds (e.g., 4h-m and 4o).
Sources & evidence
- ORD record
- ord-db43277b86a74d94b5b55ad1d14c1592
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08906908B2
Reaction notes
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