| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1346069 | Tetrahedron: Asymmetry | 2012 | 6 Pages |
A practical and enantioselective synthetic method for tapentadol has been described. Starting from inexpensive and readily available (E)-3-(3-(benzyloxy)phenyl)acrylic acid, tapentadol was prepared in seven steps (44% overall yield and 99.9% de) in more than 100 g batches, without any chromatographic purification. An Evans’ chiral auxiliary based conjugate addition and alkylation were used as the key steps.
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(R,E)-3-(3-(3-(Benzyloxy)phenyl)acryloyl)-4-phenyloxazolidin-2-oneC25H21NO4[α]D22=+4.5 (c 1.0, CHCl3)Source of chirality: (R)-4-phenyloxazolidin-2-oneAbsolute configuration: (R)
(R)-3-{(R)-3-[3-(Benzyloxy)phenyl]pentanoyl}-4-phenyloxazolidin-2-oneC27H27NO4Ee = 99.8%[α]D22=-91.2 (c 1.0, CHCl3)Source of chirality: (R)-4-phenyloxazolidin-2-oneAbsolute configuration: (R)(R)
(R)-3-{(2R,3R)-3-[3-(Benzyloxy)phenyl]-2-methylpentanoyl}-4-phenyloxazolidin-2-oneC28H29NO4Ee = 99.9%De = 99.8%[α]D22=-148.6 (c 0.5, CHCl3)Source of chirality: (R)-4-phenyloxazolidin-2-oneAbsolute configuration: (R)(2R,3R)
(2R,3R)-3-[3-(Benzyloxy)phenyl]-2-methylpentanoic acidC19H22O3[α]D22=-20.0 (c 1.0, CHCl3)Source of chirality: (R)-4-phenyloxazolidin-2-oneAbsolute configuration: (2R,3R)
(2R,3R)-3-(3-(Benzyloxy)phenyl)-N,N,2-trimethylpentanamideC21H27NO2[α]D22=-46.2 (c 1.0, CHCl3)Source of chirality: (R)-4-phenyloxazolidin-2-oneAbsolute configuration: (2R,3R)
(2R,3R)-3-[3-(Benzyloxy)phenyl]-N,N,2-trimethylpentan-1-amineC21H29NO[α]D22=-17.6 (c 1.0, CHCl3)Source of chirality: (R)-4-phenyloxazolidin-2-oneAbsolute configuration: (2R,3R)
3-[(2R,3R)-1-(Dimethylamino)-2-methylpentan-3-yl]phenol hydrochlorideC14H24ClNODe = 99.9%[α]D22=-29.6 (c 1.1, MeOH)Source of chirality: (R)-4-phenyloxazolidin-2-oneAbsolute configuration: (2R,3R)
