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

HRID 1297242노트

반응식

HRID 1297242 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-2725c8ccce71477eacc6fcb0bbbac680
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07250433B2

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