Sodium Carbonate → (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-phenoxyphenyl)pyridin-3-yl)acetate

HRID 718338Notes

Reaction equation

HRID 718338 reaction equation
Br[C:2]1[C:3]([N:21]2[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]2)=[C:4]([C@H:10]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:5]([CH3:9])=[N:6][C:7]=1[CH3:8].[O:29]([C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:17]([O:16][C@@H:10]([C:4]1[C:5]([CH3:9])=[N:6][C:7]([CH3:8])=[C:2]([C:39]2[CH:40]=[CH:41][C:36]([O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:37][CH:38]=2)[C:3]=1[N:21]1[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]1)[C:11]([O:13][CH2:14][CH3:15])=[O:12])([CH3:20])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343774-Phenoxyphenylboronic acidHCID 118314215Ethyl (S)-2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118314201(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-phenoxyphenyl)pyridin-3-yl)acetateYield 29.7%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A mixture of (S)-ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (0.0462 g, 0.101 mmol), (4-phenoxyphenyl)boronic acid (0.033 g, 0.152 mmol) and 2M Na2CO3 (0.127 ml, 0.254 mmol) degassed for 10 min. Then, Pd(Ph3P)4 (0.012 g, 10.14 μmol) added, degassed for 5 min and placed in a pre-heated oil bath 110° C. After 2 h, cooled and purified by pre-HPLC to afford (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-phenoxyphenyl)pyridin-3-yl)acetate (0.0162 g, 0.030 mmol, 29.3% yield) as white solid. 1H NMR (500 MHz, CDCl3 δ7.34-7.39 (m, 2H), 7.24-7.28 (m, 1H), 7.09-7.17 (m, 4H), 7.04-7.08 (m, 2H), 6.09 (s, 1H), 4.14-4.30 (m, 2H), 3.20 (d, J=12.3 Hz, 1H), 2.88 (t, J=11.7 Hz, 1H), 2.62 (s, 3H), 2.33 (d, J=11.5 Hz, 1H), 2.25 (s, 3H), 2.12 (t, J=11.4 Hz, 1H), 1.57 (dt, J=4.3, 12.5 Hz, 1H), 1.37-1.44 (m, 1H), 1.26 (t, J=7.1 Hz, 4H), 1.19-124 (m, 1H), 1.22 (s, 9H), 1.12 (d, J=12.1 Hz, 1H), 0.93 (s, 3H), 0.72 (s, 3H). LCMS (M+H)=545.4.

Workup

  1. customdegassed for 10 min
  2. customdegassed for 5 min
  3. customplaced in a pre-heated oil bath 110° C
  4. temperaturecooled
  5. custompurified by pre-HPLC

Sources & evidence

ORD record
ord-b8c0d7a1af0b4f5994a6543e3e0a3ba0
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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