Phthalimide → 1,1-dimethylethyl (1S,4S,6S)-4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3-azabicyclo[4.1.0]heptane-3-carboxylate

HRID 1094765Notes

Reaction equation

O[CH2:2][C@@H:3]1[CH2:9][C@H:8]2[C@H:6]([CH2:7]2)[CH2:5][N:4]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:36]1(=[O:46])[NH:40][C:39](=[O:41])[C:38]2=[CH:42][CH:43]=[CH:44][CH:45]=[C:37]12.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.O>[O:41]=[C:39]1[C:38]2[C:37](=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:36](=[O:46])[N:40]1[CH2:2][C@@H:3]1[CH2:9][C@H:8]2[C@H:6]([CH2:7]2)[CH2:5][N:4]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11]

Participants

Conditions

Temperature: 50 °C

Procedure

1,1-dimethylethyl (1S,4S,6S)-4-(hydroxymethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate D27 (310 mg), triphenylphosphine (1073 mg, 4.09 mmol) and phthalimide (502 mg, 3.41 mmol) were collected together and dissolved in THF (7 ml). The mixture was brought to 50° C. and then DIAD (0.796 ml, 4.09 mmol) was added dropwise. The mixture was stirred for 1 hour at 50° C. then 1 ml of water were added. Volatiles were removed in vacuum and the resulting crude was purified by silica gel chromatography (column size 10 g) using Cy/EtOAc=8:2 to Cy/EtOAc=5:5 to EtOAc 100%. It was recovered the title compound D28 (488 mg). UPLC: (Acid Final_QC): rt=0.80 minutes, peaks observed: 357 (M+1). C20H24N2O4 requires 356.

Workup

customwas brought to 50° C.
customVolatiles were removed in vacuum
customthe resulting crude was purified by silica gel chromatography (column size 10 g)
customIt was recovered the title compound D28 (488 mg)
customrt=0.80 minutes, peaks

Sources & evidence

ORD record: ord-51d2742b25e34c82a57eededefbac51e
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08133908B2

Reaction notes

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