Reaction #58583

ord-767ee72b508949e0b1fe683c50924b03

Reaction equation

O=C1OC[C@@H](Cc2ccccc2)N1C(=O)[C@H](CC1CCCC1)[C@@H](O)CCc1ccccc1

( 3 )

3-(2(R)-cyclopentylmethyl-3(S)-hydroxyl-5-phenyl-1-oxopentyl)-4(R)-(phenylmethyl)-2-oxazolidinone

3-(3,5-difluorophenyl)propanal

O=C(N[C@H]1CCCCN(Cc2cccc(Oc3ccccc3)c2)C1=O)[C@H](CC1CC1)[C@@H](O)CCc1cc(F)cc(F)c1

( 2 )

2(R)-cyclopropylmethyl-5-(3,5-difluorophenyl)-3-(S)-hydroxypentanoic acid (2-oxo-1-(3-phenoxybenzyl)azapan-3-(S)-yl)amide

trans-3,5-difluorocinnamic acid

( 1 )

(R)-4-(phenylmethyl)-2-oxazolidinone

3-(3,5-difluorophenyl)propionic acid

→

CN1C(=O)C(NC(=O)[C@H](CC2CC2)[C@@H](O)CCc2cc(F)cc(F)c2)N=C(c2ccccn2)c2ccccc21

3-(2-(R)-cyclopropylmethyl-5-(3,5-difluorophenyl)-3(S)-hydroxyl-1-oxopentyl)amino-1-methyl-5-(pyridin-2-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one

Reactants

—

Weinreb amide

( 3 )

3-(2(R)-cyclopentylmethyl-3(S)-hydroxyl-5-phenyl-1-oxopentyl)-4(R)-(phenylmethyl)-2-oxazolidinone

3-(3,5-difluorophenyl)propanal

—

aldehyde

( 2 )

2(R)-cyclopropylmethyl-5-(3,5-difluorophenyl)-3-(S)-hydroxypentanoic acid (2-oxo-1-(3-phenoxybenzyl)azapan-3-(S)-yl)amide

trans-3,5-difluorocinnamic acid

( 1 )

(R)-4-(phenylmethyl)-2-oxazolidinone

3-(3,5-difluorophenyl)propionic acid

Reagents

None

Conditions

Detailed conditions

See reaction.notes.procedure_details.

Procedure

The 3-(3,5-difluorophenyl)propanal used in the aldol reaction was prepared from trans-3,5-difluorocinnamic acid by: (1) hydrogenation to 3-(3,5-difluorophenyl)propionic acid (L. Kruse et al J. Med. Chem. 1987, 30, 486-494); (2) formation of Weinreb amide (M. Braun Synthesis 1989, 856); and (3) reduction to aldehyde (D. A. Evans J. Org. Chem. 1993, 58, 2446-2453).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07423033B2uspto-grants-2008_09