1,2-Dichloroethane → (1-Carbamoyl-2-isobutyl-cyclopropylmethyl)-carbamic acid tert-butyl ester

HRID 1297242ノート

反応式

HRID 1297242 の反応式
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1([C:17]([OH:19])=O)[CH2:12][CH:11]1[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=[N:26]C=2C=1.CN1CCOCC1.C(Cl)CCl>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10]1([C:17](=[O:19])[NH2:26])[CH2:12][CH:11]1[CH2:13][CH:14]([CH3:16])[CH3:15])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 4

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 221827451-(Tert-butoxycarbonylamino-methyl)-2-isobutyl-cyclopropanecarboxylic acid

生成物 1

HCID 69516040(1-Carbamoyl-2-isobutyl-cyclopropylmethyl)-carbamic acid tert-butyl ester収率 69%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of 1-(tert-butoxycarbonylamino-methyl)-2-isobutyl-cyclopropanecarboxylic acid (5.2 g, 19.2 mmol) in dry THF (190 mL) was added HOBt (2.85 g, 21.1 mmol), NMM (2.32 mL, 21.1 mmol) and EDC (4.0 g, 21.1 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 3 hours and quenched with concentrated ammonium hydroxide (16 mL). The reaction mixture was stirred at room temperature overnight. Excess of solvent was removed in vacuo and the residue was dissolved in EtOAc (200 mL). The organic layer was washed with 1N HCl, aqueous NaHCO3, brine and dried over Na2SO4. Evaporation of excess of solvent gave 3.5 g (69%) of (1-carbamoyl-2-isobutyl-cyclopropylmethyl)-carbamic acid tert-butyl ester as a colorless oil: 1H NMR (300 MHz, CD3OD) & 0.61 (dd, J=4.2, 6.5 Hz, 1H), 0.94 (d, J=5.0 Hz, 3H), 0.96 (d, J=5.0 Hz, 3H), 1.20 (m, 1H), 1.29 (dd, J=3.9, 8.7 Hz, 1H), 1.44 (s, 9H), 1.51 (m, 2H), 1.65 (m, 1H), 3.20 (d, J=15.2 Hz, 1H), 3.54 (d, J=15.2 Hz, 1H); 13C (75 MHz, CD3OD) δ 21.5, 23.2, 23.6, 27.4, 29.3, 30.3, 30.4, 39.3, 41.8, 80.9, 159.3, 179.9; MS (APCI) m/z271 [M+H]+.

後処理

  1. customquenched with concentrated ammonium hydroxide (16 mL)
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. customExcess of solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in EtOAc (200 mL)
  5. washThe organic layer was washed with 1N HCl, aqueous NaHCO3, brine
  6. dry with materialdried over Na2SO4
  7. customEvaporation of excess of solvent

出典と根拠

ORDレコード
ord-2725c8ccce71477eacc6fcb0bbbac680
出典データセット
uspto-grants-2007_07
特許番号
US07250433B2

反応ノート

読み込み中…