反应 #554669

反应方程式

LAH

methyl 4-benzyl-3-methyl-5-oxo-1,4-oxazepane-6-carboxylate

LAH

→

(4-benzyl-3-methyl-1,4-oxazepan-6-yl)methanol

溶剂

THF

THF

反应条件

后处理

1. 1
   温度the mixture was heated at 60° C. for 4 h
2. 2
   温度The mixture was cooled to 0° C.
3. 3
   其他excess LAH was quenched with 100 uL of H2O
4. 4
   workup.ADDITIONThe mixture was diluted with EtOAc (100 mL)
5. 5
   过滤filtered
6. 6
   浓缩The filtrate was concentrated
7. 7
   其他the residue purified by reverse phase liquid chromatography (H2O/CH3CN gradient w/0.1% TFA present)

实验过程

A solution of LAH in THF (2.0 M, 3.25 mL, 6.49 mmol, 3.00 equiv) was added to a solution of methyl 4-benzyl-3-methyl-5-oxo-1,4-oxazepane-6-carboxylate (4-4, diastereomeric mixture, 600 mg, 2.16 mmol, 1 equiv) in THF (30 mL) at −78° C. and the resulting mixture was warmed to 23° C. and stirred for 60 h. Additional LAH solution (2.0 M, 3.25 mL, 6.49 mmol, 3.00 equiv) was added and the mixture was heated at 60° C. for 4 h. The mixture was cooled to 0° C. and excess LAH was quenched with 100 uL of H2O, followed by 100 uL of 15% aqueous sodium hydroxide solution, and lastly 300 uL of H2O. The mixture was diluted with EtOAc (100 mL) and filtered. The filtrate was concentrated and the residue purified by reverse phase liquid chromatography (H2O/CH3CN gradient w/0.1% TFA present) to afford (4-benzyl-3-methyl-1,4-oxazepan-6-yl)methanol (4-5) as a mixture of diastereomers (TFA salts). 1H NMR (300 MHz, CD3OD) δ 7.62-7.45 (m, 5H), 4.70-4.30 (br m, 2H), 4.10-3.75 (br m, 3H), 3.65-3.30 (br m, 6 H), 2.45 (m, 1H), 1.45 (d, 3H,J=7.3 Hz). LRMS m/z (M+H) 236.3 found, 236.2 required. The TFA salts were free based by elution through an ion exchange column (Strata™ X-C, water loading, washing with CH3OH followed by elution of free base with 5% NH4OH in methanol).

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