1,2-Dichloroethane → (R)-tert-butyl 4-(5-(3,4-diethoxybenzyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylcarbamate

HRID 1053767ノート

反応式

HRID 1053767 の反応式
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH2:13][C:14]([OH:16])=O)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.O[NH:32][C:33]([C:35]1[CH:43]=[CH:42][CH:41]=[C:40]2[C:36]=1[CH2:37][CH2:38][C@H:39]2[NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[NH:34]>CN(C=O)C.C([O-])(O)=O.[Na+]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH2:13][C:14]1[O:16][N:34]=[C:33]([C:35]2[CH:43]=[CH:42][CH:41]=[C:40]3[C:36]=2[CH2:37][CH2:38][C@H:39]3[NH:44][C:45](=[O:51])[O:46][C:47]([CH3:49])([CH3:48])[CH3:50])[N:32]=1)[CH3:2]

参加物

7

反応物 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5798133,4-Diethoxyphenylacetic acidHCID 178453866HCID 178453866、化合物

生成物 1

HCID 67197789(R)-tert-butyl 4-(5-(3,4-diethoxybenzyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylcarbamate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
80 °C

実験手順

Prepared using General Procedure 2. A solution of 2-(3,4-diethoxyphenyl)acetic acid (150.0 mg, 0.67 mmol) in DMF (3 mL) was treated with HOBt (164.8 mg, 1.22 mmol) and EDC (172.7 mg, 0.9 mmol) at room temperature. The reaction was stirred for 2 h until the complete formation of the HOBt-acid complex. (R)-tert-butyl 4-(N-hydroxycarbamimidoyl)-2,3-dihydro-1H-inden-1-ylcarbamate INT-54 (233.8 mg, 0.8 mmol) was added and stirred at room temperature for 2 h and then mixture was heated to 80° C. for 16 h. The reaction was diluted with NaHCO3 (10 mL) and extracted with EA (3×10 ml). The organic phase was dried over MgSO4 and the crude product was purified by a chromatography (EA/hexanes) to produce (R)-tert-butyl 4-(5-(3,4-diethoxybenzyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylcarbamate INT-56 (187 mg, 58%) as off-white solid and used directly in the next step. LCMS-ESI (m/z) calculated for C27H33N3O5: 479.2; found 502.2 [M+Na]+, tR=4.11 min. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J=7.6 Hz, 1H), 7.39 (d, J=7.5 Hz, 1H), 7.27 (t, J=7.7 Hz, 1H), 6.81 (ddd, J=20.2, 12.8, 5.1 Hz, 3H), 5.18 (d, J=8.4 Hz, 1H), 4.69 (d, J=8.3 Hz, 1H), 4.15 (d, J=6.1 Hz, 2H), 4.06-3.93 (m, 4H), 3.32 (ddd, J=17.4, 8.8, 3.4 Hz, 1H), 3.14-2.91 (m, 1H), 2.65-2.40 (m, 1H), 1.75 (dq, J=12.9, 8.4 Hz, 1H), 1.36 (ddd, J=40.2, 26.9, 22.6 Hz, 15H).

後処理

  1. customPrepared
  2. addition(233.8 mg, 0.8 mmol) was added
  3. stirringstirred at room temperature for 2 h
  4. extractionextracted with EA (3×10 ml)
  5. dry with materialThe organic phase was dried over MgSO4
  6. customthe crude product was purified by a chromatography (EA/hexanes)

出典と根拠

ORDレコード
ord-a81bb5bfc75f4bd987102ff02a70393a
出典データセット
uspto-grants-2016_07
特許番号
US09394264B2

反応ノート

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