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

HRID 718349Notes

Reaction equation

HRID 718349 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].[CH3:35][C:36]([CH3:41])([CH3:40])[CH2:37][CH2:38]O.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][CH2:38][CH2:37][C:36]([CH3:41])([CH3:40])[CH3:35])=[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 122333,3-Dimethyl-1-butanolHCID 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 118314220(S)-ethyl 2-(tert-butoxy)-2-(5-(4-(3,3-dimethylbutoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetateYield 41.4%

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 (0.042 g, 0.090 mmol), 3,3-dimethylbutan-1-ol (0.046 g, 0.448 mmol) and Ph3P (0.071 g, 0.269 mmol) in THF (5 mL) was added DEAD (0.043 ml, 0.269 mmol) at 0° C. After 1 h, cold bath was removed and stirred overnight (15 h) at rt. Then, reaction mixture was concentrated and purified by prep-HPLC to afford (S)-ethyl 2-(tert-butoxy)-2-(5-(4-(3,3-dimethylbutoxyl)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate (0.0205 g, 0.037 mmol, 41.4% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.14-7.17 (m, 1H), 7.05-7.09 (m, 1H), 6.95-6.99 (m, 2H), 6.09 (s, 1H), 4.27 (qd, J=7.1, 10.8 Hz, 1H), 4.17 (qd, J=7.1, 10.7 Hz, 1H), 4.08-4.13 (m, 2H), 3.19 (d, J=11.8 Hz, 1H), 2.88 (t, J=12.1 Hz, 1H), 2.61 (s, 3H), 2.28 (d, J=11.8 Hz, 1H), 2.21 (s, 3H), 2.07 (t, J=11.8 Hz, 1H), 1.79 (t, J=7.3 Hz, 2H), 1.56 (td, J=3.7, 12.4 Hz, 1H), 1.34-1.42 (td, J=3.5, 12.5 Hz, 1H), 1.26 (t, J=7.1 Hz, 3H), 1.21 (s, 9H), 1.17-1.20 (m, 1H), 1.08 (d, J=12.9 Hz, 1H), 1.04 (s, 9H), 0.90 (s, 3H), 0.66 (s, 3H). LCMS (M+H)=553.4.

Workup

  1. customcold bath was removed
  2. customThen, reaction mixture
  3. concentrationwas concentrated
  4. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-1daba3f5e08e446d828c5faf60be6c24
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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