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

HRID 718353Notes

Reaction equation

HRID 718353 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].[F:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42][CH:43](O)[CH3:44])=[CH:38][CH:37]=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][CH:43]([CH3:44])[CH2:42][C:39]3[CH:40]=[CH:41][C:36]([F:35])=[CH:37][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 5462977Diethyl azodicarboxylateHCID 111827201-(4-Fluorophenyl)propan-2-olHCID 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 118314217(2S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((1-(4-fluorophenyl)propan-2-yl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetateYield 67.2%

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 (0.09 g, 0.192 mmol), 1-(4-fluorophenyl)propan-2-ol (0.08 g, 0.519 mmol) and Ph3P (0.151 g, 0.576 mmol) in THF (5 mL) was added DEAD (0.091 ml, 0.576 mmol) at 0° C. After 2 h, cold bath was removed and stirred for 15 h at rt. Then, purified by prep-HPLC to afford (2S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((1-(4-fluorophenyl)propan-2-yl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.0778 g, 0.129 mmol, 67.0% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.27-7.21 (m, 2H), 7.15 (dd, J=8.6, 2.3 Hz, 1H), 7.07 (dt, J=8.2, 2.1 Hz, 1H), 7.03-6.93 (m, 4H), 6.08 (s, 1H), 4.63 (qd, J=6.1, 3.8 Hz, 1H), 4.26 (dq, J=10.8, 7.1 Hz, 1H), 4.17 (dq, J=10.9, 7.1 Hz, 1H), 3.18 (d, J=11.0 Hz, 1H), 3.08 (dd, J=13.9, 6.0 Hz, 1H), 2.93-2.83 (m, 2H), 2.61 (s, 3H), 2.27 (d, J=8.8 Hz, 1H), 2.22 (s, 3H), 2.04 (t, J=11.7 Hz, 1H), 1.67-1.60 (m, 1H), 1.59-1.51 (m, 1H), 1.36 (d, J=6.1 Hz, 3H), 1.34 (d, J=6.1 Hz, 3H), 1.26 (t, J=7.2 Hz, 3H), 1.21 (s, 9H), 1.19-1.15 (m, 1H), 1.09-1.03 (m, 1H), 0.90 (br. s., 3H), 0.62 (br. s., 3H). LCMS (M+H)=605.4.

Workup

  1. customcold bath was removed
  2. customThen, purified by prep-HPLC

Sources & evidence

ORD record
ord-643f4f09464f44ffb246d0f7064da8aa
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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