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Triphenylphosphine → (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-(2,4,5-trifluorophenethoxy)phenyl)pyridin-3-yl)acetic acid

HRID 718453
ノート
印刷プレビュー

反応式

HRID 718453 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].[F:35][C:36]1[CH:41]=[C:40]([F:42])[C:39]([F:43])=[CH:38][C:37]=1[CH2:44][CH2:45][OH:46].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH-].[Na+]>C1COCC1.CO>[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:46][CH2:45][CH2:44][C:37]3[CH:38]=[C:39]([F:43])[C:40]([F:42])=[CH:41][C:36]=3[F:35])=[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 5363146Diisopropyl azodicarboxylateHCID 177508392-(2,4,5-Trifluorophenyl)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 118307808
(S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-(2,4,5-trifluorophenethoxy)phenyl)pyridin-3-yl)acetic acid
収率 79.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒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 (25 mg, 0.053 mmol), 2-(2,4,5-trifluorophenyl)ethanol (47.0 mg, 0.267 mmol) and Ph3P-resin (69.7 mg, 0.267 mmol) in THF (2 mL) was added DIAD (0.052 mL, 0.267 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1N NaOH (0.854 mL, 0.854 mmol) in MeOH (1 mL) at 75° C. for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-(2,4,5-trifluorophenethoxy)phenyl)pyridin-3-yl)acetic acid (25.2 mg, 0.042 mmol, 79% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.60-7.46 (m, 2H), 7.21 (d, J=8.4 Hz, 1H), 7.08-6.87 (m, 3H), 5.85 (br. s., 1H), 4.26 (q, J=6.2 Hz, 2H), 3.23 (br. s., 1H), 3.07 (t, J=6.2 Hz, 2H), 2.85-2.73 (m, 1H), 2.43 (s, 3H), 2.16 (br. s., 1H), 2.05 (s, 3H), 1.96-1.86 (m, 1H), 1.48 (br. s., 1H), 1.29 (br. s., 1H), 1.17 (d, J=13.6 Hz, 1H), 1.13 (s, 9H), 1.01 (d, J=12.5 Hz, 1H), 0.84 (br. s., 3H), 0.59 (br. s., 3H). LCMS (M+H)=599.2.

後処理

  1. filtrationmixture was filtered
  2. customto remove polymer
  3. concentrationconcentrated
  4. temperatureMixture was then cooled
  5. custompurified by prep-HPLC

出典と根拠

ORDレコード
ord-9440d5e7ec284451ad949cddc319551a
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09193720B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート