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

HRID 718350Notes

Reaction equation

HRID 718350 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][O:36][C:37]1[CH:42]=[CH:41][C:40]([CH2:43][CH2:44]O)=[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][CH2:44][CH2:43][C:40]3[CH:41]=[CH:42][C:37]([O:36][CH3:35])=[CH:38][CH:39]=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 697054-Methoxyphenethyl 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 118314221(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-methoxyphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetateYield 70.6%

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), 2-(4-methoxyphenyl)ethanol (0.065 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-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-methoxyphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.0362 g, 0.060 mmol, 70.4% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.27-7.23 (m, 2H), 7.17-7.13 (m, 1H), 7.09-7.04 (m, 1H), 7.00-6.95 (m, 2H), 6.92-6.88 (m, 2H), 6.08 (s, 1H), 4.29-4.12 (m, 4H), 3.83 (s, 3H), 3.18 (br. s., 1H), 3.11 (t, J=7.1 Hz, 2H), 2.88 (br. s., 1H), 2.61 (s, 3H), 2.28 (br.s., 1H), 2.20 (s, 3H), 2.12-2.00 (m, 1H), 1.71-1.81 (m, 1H), 1.60-1.49 (m, 1H), 1.41-1.32 (m, 1H), 1.26 (t, J=7.1 Hz, 3H), 1.21 (s, 9H), 1.08-1.12 (m, 1H), 0.90 (br.s., 2H), 0.67 (br. s., 2H). LCMS (M+H)=603.5.

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-f7aad1d9dda0418ca99e4d60b6bc4b61
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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