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Sodium Carbonate → (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((3-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

HRID 718343
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HRID 718343 반응식
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].[F:29][C:30]1[CH:31]=[C:32]([CH:44]=[CH:45][CH:46]=1)[CH2:33][O:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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:38]2[CH:37]=[CH:36][C:35]([O:34][CH2:33][C:32]3[CH:44]=[CH:45][CH:46]=[C:30]([F:29])[CH:31]=3)=[CH:40][CH:39]=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]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 16218125(4-((3-Fluorobenzyl)oxy)phenyl)boronic acidHCID 118314215Ethyl (S)-2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate

생성물 1

HCID 118314209(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((3-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate수율 64.9%

시약·촉매·용매 2

HCID 178418397
HCID 178418397, 화합물
촉매
HCID 6228Dimethylformamide용매

실험 절차

A mixture of (S)-ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (0.0443 g, 0.097 mmol), (4-((3-fluorobenzyl)oxy)phenyl)boronic acid (0.036 g, 0.146 mmol) and 2M Na2CO3 (0.122 ml, 0.243 mmol) in DMF 92 mL) was degassed for 10 min. Then, Pd(Ph3P)4 (0.011 g, 9.73 μmol) was added, degassed for 5 min and placed in a oil bath pre-heated to 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)-5-(4-((3-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.0361 g, 0.063 mmol, 64.3% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.39 (dt, J=5.8, 7.9 Hz, 1H), 7.24-7.27 (m, 1H), 7.22 (dd, J=2.1, 9.5 Hz, 1H), 7.17-7.20 (m, 1H), 7.02-7.10 (m, 4H), 6.03 (br. s., 1H), 5.12-5.20 (m, 2H), 4.23-4.31 (m, 1H), 4.19 (qd, J=7.1, 10.7 Hz, 1H), 3.06-3.28 (m, 1H), 2.85 (br. s., 1H), 2.65 (br. s., 3H), 2.26 (br. s., 3H), 1.96-2.11 (m, 1H), 1.27 (t, J=7.1 Hz, 4H), 1.20 (s, 9H), 0.90 (br.s., 3H), 0.66 (br. s., 3H). 5H of piperidine were not resolved. LCMS (M+H)=577.4.

후처리

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

출처 및 근거

ORD 기록
ord-09eac1b239904d5ab0983b845a69d181
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09193720B2

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