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

Reaktionsgleichung

Reaktionsgleichung von HRID 1053767
[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]

Komponenten

7

Edukt 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5798133,4-Diethoxyphenylacetic acidHCID 178453866HCID 178453866, Verbindung

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-a81bb5bfc75f4bd987102ff02a70393a
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394264B2

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