Bromine → 2-(1-(4-Bromophenyl)-3-(1,3-dioxan-2-yl)-1-oxopropan-2-yl) 1-tert-butyl pyrrolidine-1,2-dicarboxylate

HRID 80390Notes

Reaction equation

HRID 80390 reaction equation
BrBr.[Br:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:19])[CH2:11][CH2:12][CH:13]2[O:18][CH2:17][CH2:16][CH2:15][O:14]2)=[CH:6][CH:5]=1.[C:20]([N:27]1[CH2:34][CH2:33][CH2:32][C@H:28]1[C:29]([OH:31])=[O:30])([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].CCN(C(C)C)C(C)C>C(OCC)C.O1CCOCC1>[N:27]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:34][CH2:33][CH2:32][CH:28]1[C:29]([O:31][CH:11]([CH2:12][CH:13]1[O:14][CH2:15][CH2:16][CH2:17][O:18]1)[C:10]([C:7]1[CH:8]=[CH:9][C:4]([Br:3])=[CH:5][CH:6]=1)=[O:19])=[O:30]

Participants

7

Reactant 4

HCID 24408BromineHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 114720634'-Bromo-3-(1,3-dioxan-2-YL)propiophenone

Product 1

HCID 686255212-(1-(4-Bromophenyl)-3-(1,3-dioxan-2-yl)-1-oxopropan-2-yl) 1-tert-butyl pyrrolidine-1,2-dicarboxylateYield 100%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
24 °C

Procedure

Bromine (1.3 mL, 25.2 mmol) was added to a solution of Example J2, 1-(4-bromophenyl)-3-(1,3-dioxan-2-yl)propan-1-one (7.7 g, 25.7 mmol) in diethyl ether (60 mL) and 1,4-dioxane (40 mL) and the solution stirred 30 min at 24° C. (Until TLC indicated reaction complete). The solvent was removed by rotory evaporation and the residue was taken up in acetonitrile (350 mL). (S)—N-Boc-Proline (5.54 g, 25.7 mmol) was added followed by dropwise addition of Hunig's base (8.5 mL, 51.5 mmol) and the reaction was stirred 6 hours before being concentrated. The crude product was taken up in CH2Cl2 and charged to a 40 (M) Biotage silica gel cartridge. Gradient elution 15-100% B over 1 L (A=hexanes; B=ethyl acetate) gave Example J3, 2-(1-(4-bromophenyl)-3-(1,3-dioxan-2-yl)-1-oxopropan-2-yl) 1-tert-butyl pyrrolidine-1,2-dicarboxylate 13 g (100%).). RT=2 2 minutes (condition 1); LCMS: Anal. C23H30BrNO7 Calcd. 534; found: 534 (M+Na)+.

Workup

  1. custom(Until TLC indicated reaction complete)
  2. customThe solvent was removed by rotory evaporation
  3. stirringthe reaction was stirred 6 hours
  4. concentrationbefore being concentrated
  5. additioncharged to a 40 (M) Biotage silica gel cartridge
  6. washGradient elution 15-100% B over 1 L (A=hexanes

Sources & evidence

ORD record
ord-943c7affde9c4c2b9da1c0604b33c036
Source dataset
uspto-grants-2014_09
Patent number
US08846023B2

Reaction notes

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