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

HRID 505195

Reaktionsgleichung

Reaktionsgleichung von HRID 505195
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]

Komponenten

8

Edukt 5

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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]+.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-34337a3e7bbd42dcb02b977f86f402f3
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07781438B2

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