Acetic Acid → (7-{[(2-Fluoro-ethyl)-amino]methyl}-2-chloro-naphthalen-1-yl)-acetic acid ethyl ester

HRID 505195노트

반응식

HRID 505195 반응식
Cl.[F:2][CH2:3][CH2:4][NH2:5].[CH2:6]([O:8][C:9](=[O:24])[CH2:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH:21]=O)[CH:19]=2)[CH:14]=[CH:13][C:12]=1[Cl:23])[CH3:7].C(N(CC)CC)C.C([BH3-])#N.[Na+].C(O)(=O)C>C1COCC1.CO>[CH2:6]([O:8][C:9](=[O:24])[CH2:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH2:21][NH:5][CH2:4][CH2:3][F:2])[CH:19]=2)[CH:14]=[CH:13][C:12]=1[Cl:23])[CH3:7]

참가 물질

8

반응물 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 9995Ethanamine, 2-fluoro-, hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 86061793(2-Chloro-7-formyl-naphthalen-1-yl)-acetic acid ethyl ester

생성물 1

HCID 86625787(7-{[(2-Fluoro-ethyl)-amino]methyl}-2-chloro-naphthalen-1-yl)-acetic acid ethyl ester

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

2-Fluoroethylamine hydrochloride (94 mg, 0.94 mmol) is added under an atmosphere of argon to a solution of (2-chloro-7-formyl-naphthalen-1-yl)-acetic acid ethyl ester (200 mg, 0.72 mmol) in 7.6 ml of THF. Triethylamine (0.13 ml, 0.94 mmol) is added, and the mixture is stirred at RT for 18 h, before a solution of sodium cyanoborohydride (50 mg, 0.80 mmol) in MeOH (2.0 ml) and glacial acetic acid (0.21 ml, 3.61 mmol) are added. After stirring at RT for 1 h, TLC analysis indicates complete consumption of starting material. The reaction mixture is diluted with water and adjusted to pH 8 by the addition of a 1 M aqueous solution of NaHCO3. Extraction with EtOAc, washing with brine, drying over Na2SO4 and removal of solvent yields the crude reaction product. Purification by FCC (EtOAc/MeOH 9:1) affords the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.26 (t, J=8.4 Hz, 3H), 2.92-3.04 (m, 2H), 4.06 (s, 2H), 4.19 (q, J=8.4 Hz, 2H), 4.32 (s, 2H), 4.52-4.68 (m, 2H), 7.48 (d, J=9 Hz, 1H), 7.51-7.53 (m, 1H), 7.73 (d, J=9.4 Hz, 1H), 7.82 (d, J=9 Hz, 1H), 7.88 (s, 1H). ES+-MS: 324.2, 326.1 [M+H]+.

후처리

  1. additionare added
  2. customconsumption of starting material
  3. additionThe reaction mixture is diluted with water
  4. additionadjusted to pH 8 by the addition of a 1 M aqueous solution of NaHCO3
  5. extractionExtraction with EtOAc
  6. washwashing with brine
  7. dry with materialdrying over Na2SO4 and removal of solvent
  8. customyields the crude
  9. customreaction product
  10. customPurification by FCC (EtOAc/MeOH 9:1)

출처 및 근거

ORD 기록
ord-34337a3e7bbd42dcb02b977f86f402f3
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07781438B2

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