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

HRID 718347Notes

Reaction equation

HRID 718347 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][CH2:43]O)=[CH:38][C:37]=1[CH3:45].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][CH2:43][CH2:42][C:39]3[CH:40]=[CH:41][C:36]([F:35])=[C:37]([CH3:45])[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 27590204-Fluoro-3-methylphenethyl 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 118314212(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-fluoro-3-methylphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetateYield 72.9%

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), 2-(4-fluoro-3-methylphenyl)ethanol (0.066 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 7 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-fluoro-3-methylphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.0374 g, 0.062 mmol, 72.4% yield) as glassy paste. 1H NMR (500 MHz, CDCl3) δ 7.12-7.17 (m, 2H), 7.06-7.12 (m, 2H), 6.95-7.00 (m, 3H), 6.08 (s, 1H), 4.14-4.30 (m, 4H), 3.19 (d, J=11.2 Hz, 1H), 3.09 (t, J=7.0 Hz, 2H), 2.87 (t, J=12.0 Hz, 1H), 2.61 (s, 3H), 2.30 (d, J=1.9 Hz, 3H), 2.25-2.29 (m, 1H), 2.20 (s, 3H), 2.06 (t, J=11.7 Hz, 1H), 1.52-1.58 (m, 1H), 1.33-1.42 (m, 1H), 1.26 (t, J=7.1 Hz, 3H), 1.21 (s, 9H), 1.16-1.20 (m, 1H), 1.05-1.10 (m, 1H), 0.90 (s, 3H), 0.66 (s, 3H). LCMS (M+H)=605.3.

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-ad93b1a2333941c8917dff8c0fd6ae9a
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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