Water → 1-tert-butyl 2-methyl (2S,4R)-4-[(8-bromophenanthridin-6-yl)oxy]pyrrolidine-1,2-dicarboxylate

HRID 1423366Notes

Reaction equation

[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([OH:16])[N:6]=[C:7]3[C:12]=2[CH:11]=[CH:10][CH:9]=[CH:8]3)[CH:3]=1.BrC1C=CC(S(O[C@@H:28]2[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@H:30]([C:40]([O:42][CH3:43])=[O:41])[CH2:29]2)(=O)=O)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN1C(=O)CCC1.CCOC(C)=O>[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([O:16][C@H:28]3[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@H:30]([C:40]([O:42][CH3:43])=[O:41])[CH2:29]3)[N:6]=[C:7]3[C:12]=2[CH:11]=[CH:10][CH:9]=[CH:8]3)[CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of the product mixture from Step 2 (176 mg, 0.642 mmol) in NMP (1.5 mL) was added 1-tert-butyl 2-methyl (2S,4S)-4-{[(4-bromophenyl)sulfonyl]oxy}pyrrolidine-1,2-dicarboxylate (373 mg, 0.803 mmol) and Cs2CO3 (418 mg, 1.29 mmol). The mixture was then heated to 60° C. for 18 h, and worked up with water and EtOAc. The organic layer was washed with brine, dried over MgSO4, and the solvent was removed in vacuo. The crude material was purified on silica (gradient elution, 10-50% EtOAc/hex) to yield the title compound as a 1:1 mixture with the expected regioisomer. LRMS ((M-Boc)+H)+=401.2.

Workup

washThe organic layer was washed with brine
dry with materialdried over MgSO4
customthe solvent was removed in vacuo
customThe crude material was purified on silica (gradient elution, 10-50% EtOAc/hex)

Sources & evidence

ORD record: ord-a0f9ef40cd2e4bb9bb97c11b293e13d0
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927569B2

Reaction notes

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