tert-Butyl acetate → (S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 472876ノート

反応式

HRID 472876 の反応式
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:21])[C:3]=1[C@H:22]([OH:27])[C:23]([O:25][CH3:26])=[O:24].C(O[C:32]([CH3:35])([CH3:34])[CH3:33])(=O)C.Cl(O)(=O)(=O)=O>C(Cl)Cl>[C:32]([O:27][C@@H:22]([C:3]1[C:4]([CH3:21])=[N:5][C:6]2[N:7]([N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=2)[C:2]=1[Cl:1])[C:23]([O:25][CH3:26])=[O:24])([CH3:35])([CH3:34])[CH3:33]

参加物

5

反応物 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 86670288(S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

生成物 1

HCID 86670289(S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate収率 72.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a stirred solution of (S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (888 mg, 2.301 mmol) in CH2Cl2 (45 mL) and t-butyl acetate (21.76 mL, 161 mmol) at rt was added perchloric acid (0.593 mL, 6.90 mmol). After 2.5 h, the reaction mixture was diluted with CH2Cl2 (50 mL), carefully quenched with sat. NaHCO3 (50 mL), organic layer separated and washed with brine (100 mL), dried (Na2SO4), filtered and concentrated to give yellow liquid. This was purified by flash column chromatography on silica gel column using (10-40% EtOAc/Hex as eluant) to afford the desired (S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (735 mg, 1.663 mmol, 72.3% yield) as white solid. 150 mg of starting material was also recovered. 1H NMR (500 MHz, CDCl3) δ: 7.76-7.70 (m, 2H), 7.18 (d, J=7.9 Hz, 1H), 6.91 (s, 1H), 5.68 (s, 1H), 3.76 (s, 3H), 2.89-2.84 (m, 4H), 2.68 (s, 3H), 1.89-1.83 (m, 4H), 1.30 (s, 9H). LCMS (M+H)=444.3.

後処理

  1. customcarefully quenched with sat. NaHCO3 (50 mL), organic layer
  2. customseparated
  3. washwashed with brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give yellow liquid
  8. customThis was purified by flash column chromatography on silica gel column

出典と根拠

ORDレコード
ord-91de0fe2a18846b4b3ab1a212669979c
出典データセット
uspto-grants-2014_01
特許番号
US08633200B2

反応ノート

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