反応 #12045

反応方程式

6-acetyl-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

borane dimethylsulfide

→

6-((1S)-1-hydroxy-ethyl)-(4R,9aR)-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.STIRRINGA solution was stirred at 0° C. for 3 hours
2. 2
   その他quenched with methanol
3. 3
   その他partitioned between aqueous ammonium chloride and EtOAc
4. 4
   その他The phases were separated
5. 5
   洗浄the organic layer was washed with brine
6. 6
   乾燥dried (MgSO4)
7. 7
   濃縮concentrated in vacuo
8. 8
   その他The residue was purified by column chromatography [SiO2; isohexane-ethyl acetate (1:1)]

実験手順

To a stirred solution of (R)-Me-CBS-oxazaborolidine (770 μl, 1M in toluene) in THF (3 ml) was added borane-dimethylsulfide (770 μl, 2M in THF) at 0° C. under nitrogen. A solution was stirred for 5 mins, then 6-acetyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 34, intermediate b) (255 mg) in THF (2.5 ml) was added dropwise over 45 mins. A solution was stirred at 0° C. for 3 hours, quenched with methanol and partitioned between aqueous ammonium chloride and EtOAc. The phases were separated and the organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography [SiO2; isohexane-ethyl acetate (1:1)] to afford 6-((1S)-1-hydroxy-ethyl)-(4R,9aR)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (185 mg) as a colorless 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) and 1.24 (3H, d, J 6.5 HZ); MS (ES) 334.3 (MH+).

出典