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

HRID 1968709ノート

反応式

HRID 1968709 の反応式
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]

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-daa4e7df022f43d48d2d463f5851f863
出典データセット
uspto-grants-2013_04
特許番号
US08426440B2

反応ノート

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