Triphenylphosphine → HCID 118307736、化合物

HRID 718456ノート

反応式

HRID 718456 の反応式
[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](O)=[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]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:35][C:36]1[C:40]([CH2:41][CH2:42][OH:43])=[C:39]([CH3:44])[O:38][N:37]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>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:43][CH2:42][CH2:41][C:40]3[C:36]([CH3:35])=[N:37][O:38][C:39]=3[CH3:44])=[CH:30][CH:31]=2)[C:17]=1[N:18]1[CH2:19][CH2:20][C:21]([CH3:25])([CH3:24])[CH2:22][CH2:23]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 127623462-(3,5-Dimethyl-1,2-oxazol-4-yl)ethan-1-olHCID 118314205(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate

生成物 1

HCID 118307736HCID 118307736、化合物収率 41.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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 (50 mg, 0.107 mmol), 2-(3,5-dimethylisoxazol-4-yl)ethanol (75 mg, 0.533 mmol) and Ph3P-resin (139 mg, 0.533 mmol) in THF (2 mL) was added DIAD (0.104 mL, 0.533 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1NNaOH (1.067 mL, 1.067 mmol) in MeOH (2 mL) at 75° C. for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(5-(4-(2-(3,5-dimethylisoxazol-4-yl)ethoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid (25 mg, 0.044 mmol, 41.6% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.20 (d, J=8.8 Hz, 1H), 7.07-6.92 (m, 3H), 5.75 (s, 1H), 4.17-4.01 (m, 2H), 3.41 (br. s., 1H), 3.17 (s, 2H), 2.79 (t, J=6.2 Hz, 2H), 2.42 (s, 3H), 2.34 (s, 3H), 2.21 (s, 3H), 2.17 (d, J=12.5 Hz, 1H), 2.06-2.02 (m, 2H), 1.93 (br. s., 1H), 1.49 (br. s., 1H), 1.29 (br. s., 1H), 1.16 (d, J=13.6 Hz, 1H), 1.11 (s, 9H), 1.01 (d, J=9.9 Hz, 1H), 0.84 (br. s., 3H), 0.61 (br. s., 3H). LCMS (M+H)=564.4.

後処理

  1. filtrationmixture was filtered
  2. customto remove polymer
  3. concentrationconcentrated
  4. additiontreated with 1NNaOH (1.067 mL, 1.067 mmol) in MeOH (2 mL) at 75° C. for 16 h
  5. temperatureMixture was then cooled
  6. custompurified by prep-HPLC

出典と根拠

ORDレコード
ord-f0ad1eda54f6435bbf0bb5fc9a919851
出典データセット
uspto-grants-2015_11
特許番号
US09193720B2

反応ノート

読み込み中…