1-Hydroxybenzotriazole → (4S,7S,11aR)-7-benzoylamino-6-oxo-1,3,4,6,7,8,11,11a-octahydro-2H-pyrido[1,2-a]azocine-4-carboxylic Acid

Preparation of (4S,7S,11aR)-7-benzoylamino-6-oxo-1,3,4,6,7,8,11,11a-octahydro-2H-pyrido[1,2-a]azocine-4-carboxylic acid (2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (45) A catalytic amount of Pd(Ph3P)4 (35 mg, 0.03 mmol) is added to a solution of (2-Ethoxy-5-oxo-tetrahydrofuran-3-yl)-carbamic acid allyl ester (69 mg, 0.3 mmol) and N,N-dimethylbarbituric acid (156 mg, 1.0 mmol) in 2 mL CH2Cl2 at room temperature. The solution is stirred at rt for 15 minutes and (4S,7S,11aS)-7-benzoylamino-6-oxo-1,3,4,6,7,8,11,11a-octahydro-2H-pyrido[1,2-a]azocine-4-carboxylic acid, 44, (40 mg, 0.12 mmol) is added as a solution in 1 mL CH2Cl2, followed by 1-hydroxybenzotriazole (41 mg, 0.3 mmol) and 1-(3-dimethyl-aminopropyl)-3-ethyl-carbodiimide hydrochloride (58 mg, 0.3 mmol). The solution is stirred for 4 hours, diluted with EtOAc, washed with saturated NaHCO3 and brine, dried (MgSO4), and concentrated in vacuo. Purification by flash chromatography over silica gel afforded 32 mg of the desired product. 1H NMR (CDCl3) δ 7.88 (m, 2H), 7.72 (m, 1H), 7.51 (m, 3H), 5.75–5.25 (series of m, 4H), 5.02 (d, J=5.8 Hz, 1H), 4.66 (m, 2H), 3.98 (dq, J=9.3, 7.0 Hz, 1H), 3.73 (dq, J=9.3, 7.0 Hz, 1H), 3.24 (m, 1H), 2.96–1.45 (series of m, 11H), 1.37 (t, J=7.0 Hz, 3H); MS 470 (M+H)+.

1. stirringThe solution is stirred for 4 hours
2. washwashed with saturated NaHCO3 and brine
3. dry with materialdried (MgSO4)
4. concentrationconcentrated in vacuo
5. customPurification by flash chromatography over silica gel

ORDレコード

ord-da8aca8e73c746f4bc865eb98655fb53

出典データセット

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07138395B2