反応 #1884975

反応方程式

2(S)-tert-butoxycarbonylamino-8-nonenoic acid

4(R)-hydroxypyrrolidine-2(S)-carboxylic acid methyl ester hydrochloride

N-methyl morpholine

HATU

→

1-(2(S)-tert-Butoxycarbonylamino-non-8-enoyl)-4(R)-hydroxy-pyrrolidine-2(S)-carboxylic acid methyl ester

収率 100.0%

溶媒

ethyl acetate

ethyl acetate hexane

DCM

反応条件

後処理

1. 1
   濃縮concentrated in vacuo
2. 2
   その他The residue was partitioned between ethyl acetate and pH 4 buffer (biphthalate)
3. 3
   洗浄The organic phase was washed with sat. aq. NaHCO3
4. 4
   乾燥dried (MgSO4)
5. 5
   濃縮concentrated in vacuo
6. 6
   その他to give the crude product

実験手順

A solution of 2(S)-tert-butoxycarbonylamino-8-nonenoic acid (purchased from RSP Amino Acids)(3.5 g, 12.9 mmol) in 200 mL of DCM was treated sequentially with 4(R)-hydroxypyrrolidine-2(S)-carboxylic acid methyl ester hydrochloride (2.15 g, 11.8 mmol), N-methyl morpholine (4.25 mL, 38.6 mmol), and HATU (5.37 g, 14.1 mmol). The reaction mixture was stirred at rt under N2 for 3 days, and then concentrated in vacuo. The residue was partitioned between ethyl acetate and pH 4 buffer (biphthalate). The organic phase was washed with sat. aq. NaHCO3, dried (MgSO4), and concentrated in vacuo to give the crude product. Flash chromatography (50% ethyl acetate/hexane to 100% ethyl acetate) gave 4.7 g (˜100%) of 1-(2(S)-tert-Butoxycarbonylamino-non-8-enoyl)-4(R)-hydroxy-pyrrolidine-2(S)-carboxylic acid methyl ester as a colorless oil: 1H NMR (500 MHz, CD3OD) δ 1.33-1.50 (m, 8 H), 1.46 (s, 9 H), 1.57 (m, 1 H), 1.72 (m, 1 H) 2.08 (m, 2 H), 2.28 (m, 1 H), 3.72 (s, 3 H,) 3.75-3.87 (m, 2 H), 4.36 (m, 1 H), 4.51 (bs, 1 H), 4.57 (t, J=8.2 Hz, 1 H), 4.95 (d, J=10.4 Hz, 1 H), 5.01 (m, 1 H), 5.83 (m, 1 H); MS m/z 399 (M++1).

出典