Propanal → 9-(1-Hydroxypropyl)-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

HRID 926329Notes

Reaction equation

I[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][NH:14][C:13](=[O:18])[CH:12]=[C:7]12.C([Mg]Cl)(C)C.[CH:24](=[O:27])[CH2:25][CH3:26].[NH4+].[Cl-]>C1COCC1>[OH:27][CH:24]([C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][NH:14][C:13](=[O:18])[CH:12]=[C:7]12)[CH2:25][CH3:26]

Participants

Conditions

Temperature: -78 °C

Procedure

124-1. A mixture of 9-iodo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (2.2 g, 6.21 mmol) in dry THF (150 mL) was cooled to −78° C. under Ar, and a 2M solution of iPrMgCl in THF (18.6 mL, 37.3 mmol) was added dropwise. The mixture was stirred at −78° C. for 30 min and propionaldehyde (3.61 g, 62.1 mmol) was then added. The mixture was stirred at −78° C. for another 30 min and then allowed to warm to RT overnight. The reaction mixture was poured onto a saturated aq. solution of NH4Cl and extracted with AcOEt. The combined org. layers were then dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, heptane to AcOEt/MeOH 9:1) to give the title compound (231 mg). UPLC-MS: MS 287.2 (M+H+); UPLC rt 0.59 min.

Workup

stirringThe mixture was stirred at −78° C. for another 30 min
temperatureto warm to RT overnight
extractionextracted with AcOEt
dry with materiallayers were then dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography (SiO2, heptane to AcOEt/MeOH 9:1)

Sources & evidence

ORD record: ord-489195c551594872ba0d5e0264d8b6d3
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284331B2

Reaction notes

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