Triphenylphosphine → (S)-ethyl 2-(tert-butoxy)-2-(5-(4-((4-cyanobenzyl)oxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate

HRID 718352Notes

Reaction equation

HRID 718352 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:34])=[N:14][C:15]([CH3:33])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].O[CH2:36][C:37]1[CH:44]=[CH:43][C:40]([C:41]#[N:42])=[CH:39][CH:38]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:34])=[N:14][C:15]([CH3:33])=[C:16]([C:26]2[CH:27]=[CH:28][C:29]([O:32][CH2:36][C:37]3[CH:44]=[CH:43][C:40]([C:41]#[N:42])=[CH:39][CH:38]=3)=[CH:30][CH:31]=2)[C:17]=1[N:18]1[CH2:19][CH2:20][C:21]([CH3:24])([CH3:25])[CH2:22][CH2:23]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 160549p-Cyanobenzyl alcoholHCID 5462977Diethyl azodicarboxylateHCID 118314205(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118318371(S)-ethyl 2-(tert-butoxy)-2-(5-(4-((4-cyanobenzyl)oxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetateYield 65.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate (0.04 g, 0.085 mmol), 4-(hydroxymethyl)benzonitrile (0.057 g, 0.427 mmol) and Ph3P (0.067 g, 0.256 mmol) in THF (5 mL) was added DEAD (0.041 ml, 0.256 mmol) at 0° C. After 1 h, the cold bath was removed and stirred for 16 h at rt. Then, the reaction mixture was concentrated and the residue purified by prep-HPLC to afford (S)-ethyl 2-(tert-butoxy)-2-(5-(4-((4-cyanobenzyl)oxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate (0.0324 g, 0.056 mmol, 65.0% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.74-7.70 (m, 2H), 7.61 (d, J=8.5 Hz, 2H), 7.22-7.18 (m, 1H), 7.12-7.09 (m, 1H), 7.06-7.01 (m, 2H), 6.07 (s, 1H), 5.26-5.19 (m, 2H), 4.27 (dq, J=10.7, 7.1 Hz, 1H), 4.18 (dq, J=10.7, 7.1 Hz, 1H), 3.19 (d, J=12.1 Hz, 1H), 2.84 (t, J=12.1 Hz, 1H), 2.61 (s, 3H), 2.28 (d, J=11.3 Hz, 1H), 2.20 (s, 3H), 2.03 (t, J=11.6 Hz, 1H), 1.57-1.53 (m, 1H), 1.42-1.34 (m, 1H), 1.26 (t, J=7.1 Hz, 3H), 1.21 (s, 9H), 1.18 (br. s., 1H), 1.07 (d, J=13.4 Hz, 1H), 0.91 (s, 3H), 0.63 (s, 3H). LCMS (M+H)=584.4.

Workup

  1. customthe cold bath was removed
  2. concentrationThen, the reaction mixture was concentrated
  3. customthe residue purified by prep-HPLC

Sources & evidence

ORD record
ord-4bb785e7a6f34d129c1e2462684d0484
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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