反応 #12052

反応方程式

(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

(4R,9aR)-6-(2-hydroxy-ethoxymethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

intermediate b

(4R,9aR)-6-(2-hydroxy-ethoxymethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

n-butyllithium

acetaldehyde

→

(4R,9aR)-6-(1-hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

溶媒

THF

THF

反応条件

後処理

1. 1
   workup.STIRRINGThe solution was stirred for a further 2 hours
2. 2
   温度to warm to room temperature slowly
3. 3
   workup.STIRRINGstirred for a further 4.5 hours
4. 4
   その他The reaction was quenched with aqueous ammonium chloride (20 ml)
5. 5
   workup.ADDITIONdiluted with ethyl acetate
6. 6
   その他the phases separated
7. 7
   洗浄The organics were washed successively with water and brine
8. 8
   乾燥dried (MgSO4)
9. 9
   濃縮concentrated in vacuo
10. 10
    その他The residue was purified by column chromatography [SiO2; isohexane-ethyl acetate (3:2)]

実験手順

To a stirred solution of (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 5, intermediate b) (2 g) in THF (24 ml) at −78° C. was added n-butyllithium (2.72 ml, 2.5 M in hexanes) dropwise. The solution was stirred at −78° C. for 45 mins and acetaldehyde (604 μl) in THF (2 ml) was added dropwise. The solution was stirred for a further 2 hours, allowed to warm to room temperature slowly and stirred for a further 4.5 hours. The reaction was quenched with aqueous ammonium chloride (20 ml), diluted with ethyl acetate and the phases separated. The organics were washed successively with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography [SiO2; isohexane-ethyl acetate (3:2)] to afford (4R,9aR)-6-(1-hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (742 mg) as a yellow oil: 1H NMR (400 MHz, CDCl3) 7.16 (1H, d, J 7 Hz), 6.35 (1H, d, J 7 Hz), 4.37–4.31 (1H, br s), 4.31–4.19 (1H, br s), 4.09–3.95 (1H, m), 3.95–3.85 (1H, m), 3.13–2.94 (2H, m), 2.79–2.55 (1H, br s), 2.54 (1H, dd, J 6 and 16 Hz), 1.48 (9H, s), 1.44 (3H, d, J 6.5 Hz), 1.25 (1.5H, R epimer, d, J 6.5 Hz) and 1.24 (1.5H, S epimer, d, J 6.5 HZ); MS (ES) 334.3 (MH+).

出典