Bromoacetate → HCID 59607761, 화합물

HRID 70885노트

반응식

HRID 70885 반응식
BrCCBr.[Cl:5][C:6]1[CH:7]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C:19]#[N:20])=[C:14]([F:21])[CH:13]=2)[CH:9]=[CH:10][CH:11]=1.BrCC([O-])=O.Br[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.BrCC(OCC)=O.CCOC(C)=O.C([O-])([O-])=O.[Na+].[Na+].[Zn].CC(O)=O>[NH2:20][CH:19]([CH2:18][C:15]1[CH:16]=[CH:17][C:12]([C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([Cl:5])[CH:7]=2)=[CH:13][C:14]=1[F:21])[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30]

참가 물질

12

반응물 5

HCID 6226BromoacetateHCID 7748Ethyl bromoacetateHCID 78391,2-DibromoethaneHCID 5049666Sodium triacetoxyborohydrideHCID 59607796HCID 59607796, 화합물

생성물 1

HCID 59607761HCID 59607761, 화합물

시약·촉매·용매 6

HCID 7748Ethyl bromoacetate촉매HCID 23994Zinc촉매HCID 176Acetic Acid용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매HCID 10340Sodium Carbonate용매

반응 조건

온도
70 °C

실험 절차

A suspension of zinc (479 mg, 7.33 mmol) and 1,2-dibromoethane (0.032 ml, 0.366 mmol) in THF (8 ml) is heated at 70° C. under nitrogen then a few drops of ethyl bromoacetate is added. After stirring for 20 min, a solution of 2-(3′-chloro-3-fluorobiphenyl-4-yl)acetonitrile (300 mg, 1.221 mmol) in THF (2 ml) is added in one portion. The remaining bromoacetate is added dropwise over 50 min (total amount of ethyl bromoacetate: 4.88 mmol). After stirring for 15 min at the same temperature, the reaction mixture is cooled to ambient temperature. To the reaction mixture, sodium triacetoxyborohydride (2588 mg, 12.22 mmol) and AcOH (8 ml) are added. The reaction mixture is allowed to stir for 13 hours, and concentrated to give crude. The crude is diluted with EtOAc, and 2M aqueous Na2CO3 is added to be pH of 10. The products are extracted with EtOAc. The organic layer is dried over K2CO3, filtered, and concentrated to give crude. The resulting residue is purified by preparative HPLC using a gradient of 20% MeCN/water (0.1% NH4OH) to 100% MeCN to give ethyl 3-amino-4-(3′-chloro-3-fluorobiphenyl-4-yl)butanoate (148 mg) as orange oil; HPLC retention time=0.85 minutes (condition B); MS (m+1)=336.13; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.27 (t, J=7.1 Hz, 3 H) 2.36 (A of ABX, Jab=15.9 Hz, Jax=8.8 Hz, 1 H) 2.52 (B of ABX, Jab=15.9 Hz, Jbx=4.0 Hz, 1 H) 2.71-2.76 (m, 1 H) 2.82-2.87 (m, 1 H) 3.51-3.57 (m, 1 H) 4.15 (d, J=7.1 Hz, 2 H) 7.24-7.39 (m, 5 H) 7.42-7.44 (m, 1 H) 7.54-7.55 (m, 1 H).

후처리

  1. stirringAfter stirring for 15 min at the same temperature
  2. temperaturethe reaction mixture is cooled to ambient temperature
  3. stirringto stir for 13 hours
  4. concentrationconcentrated
  5. customto give crude
  6. additionis added
  7. extractionThe products are extracted with EtOAc
  8. dry with materialThe organic layer is dried over K2CO3
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give crude
  12. customThe resulting residue is purified by preparative HPLC

출처 및 근거

ORD 기록
ord-817ef8becd404bfe821bb0e342f21228
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822534B2

반응 노트

불러오는 중…