Triethylamine → methyl (1R,2S)-2-(4-fluoro-benzylamino)-cyclopentanecarboxylate

HRID 731264ノート

反応式

HRID 731264 の反応式
Cl.[CH3:2][O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[NH2:11])=[O:5].S([O-])([O-])(=O)=O.[Mg+2].C(N(CC)CC)C.[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=O)=[CH:28][CH:27]=1.[BH4-].[Na+].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH3:2][O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[NH:11][CH2:30][C:29]1[CH:32]=[CH:33][C:26]([F:25])=[CH:27][CH:28]=1)=[O:5]

参加物

8

反応物 6

HCID 8471TriethylamineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 680234-FluorobenzaldehydeHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 14698814119993-55-4

生成物 1

HCID 57832628methyl (1R,2S)-2-(4-fluoro-benzylamino)-cyclopentanecarboxylate収率 79.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
25 °C

実験手順

To a solution of (1R,2S)-2-amino-cyclopentanecarboxylic acid methyl ester hydrochloride (prepared as described in Example 11a, 104 mg, 0.58 mmol) in tetrahydrofuran (6 mL) at 25° C. was added magnesium sulfate (200 mg), triethylamine (0.085 mL, 0.61 mmol), and 4-fluorobenzaldehyde (0.13 mL, 1.19 mmol) sequentially. The reaction was stirred at 25° C. for 16 h. The mixture was passed through a short pad of Celite and the filtrate was concentrated and dried in vacuo. The residue was re-dissolved in methanol (10 mL) at 25° C. To this solution was added slowly sodium borohydride (45 mg, 1.19 mmol). The mixture was stirred at 25° C. for 1 h. It was then poured into a saturated sodium bicarbonate aqueous solution (10 mL) and the mixture was extracted into ethyl acetate (20 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a clear oil. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0-15% ethyl acetate in hexanes) afforded the desired product, (1R,2S)-2-(4-fluoro-benzylamino)-cyclopentanecarboxylic acid methyl ester (116 mg, 0.46 mmol, 79%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 1.55-1.73 (2H, m), 1.83-1.93 (3H, m), 1.99-2.08 (1H, m), 2.97 (1H, dd, J1=14.4 Hz, J2=8.0 Hz), 3.31 (1H, dd, J1=14.4 Hz, J2=7.2 Hz), 3.70 (3H, s), 3.77 (2H, dd, J1=19.6 Hz, J2=12.0 Hz), 4.67 (1H, s), 6.96-7.06 (2H, m), 7.26-7.35 (2H, m). LC-MS (ESI) calcd for C14H18FNO2 251.30, found 252.1 [M+H+].

後処理

  1. concentrationthe filtrate was concentrated
  2. customdried in vacuo
  3. dissolutionThe residue was re-dissolved in methanol (10 mL) at 25° C
  4. stirringThe mixture was stirred at 25° C. for 1 h
  5. extractionthe mixture was extracted into ethyl acetate (20 mL)
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a clear oil
  10. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0-15% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-d303cfff54d349ec8f26ecfdb5055db4
出典データセット
uspto-grants-2009_09
特許番号
US07582626B2

反応ノート

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