Bromine → HCID 15454950, compound

HRID 2287518Notes

Reaction equation

HRID 2287518 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C@H:15]([CH3:16])[C@H:14]([CH:17]=[O:18])[C@H:13]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@@H:12]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]([O-])(O)=[O:34].[Na+].BrBr.[O-]S([O-])(=S)=O.[Na+].[Na+]>CO.O>[CH2:1]([O:8][C:9]([N:11]1[C@H:15]([CH3:16])[C@H:14]([C:17]([O:34][CH3:33])=[O:18])[C@H:13]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@@H:12]1[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 24408Bromine2×HCID 24477Sodium ThiosulfateHCID 516892Sodium BicarbonateHCID 15454949HCID 15454949, compound

Product 1

HCID 15454950HCID 15454950, compoundYield 107.1%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent2×

Procedure

To a stirred and ice-cooled mixture of crude (2S*,3S*,4R*,5R*)-1-benzyloxycarbonyl-3-[N-(t-butoxycarbonyl)amino]-4-formyl-5-methyl-2-phenylpyrrolidine (3.66 g, 5.90 mmol) and NaHCO3 (19.8 g, 0.24mol) in MeOH--H2O (9:1 by volume; 30 ml) was added a 2.0 M solution of Br2 in MeOH--H2O (9:1; 30 ml, 60 mmol) dropwise. The reaction mixture was stirred at room temperature for 2 hours, during which the color changed from deep red to orange. Sat. Na2S2O3 (hypo) aq. solution was added dropwise to the mixture with ice-cooling, until the orange color due to the excess Br2 was discharged. The mixture was filtered through a pad of Celite, and the filter cake was washed with CH2Cl2. The combined filtrate and washings were concentrated in vacuo. The syrupy residue was diluted with AcOEt--PhMe (2:1, 120 ml), washed with sat. Na2S2O3 aq. solution (×2), sat. NaHCO3 aq. solution (×1), and sat. NaCl aq. solution, dried (MgSO4), and concentrated in vacuo to give a white solid (2.96 g). This was recrystallized from AcOEt-n-hexane to give title compound (2.44 g, 88% in 2 steps from (2S*,3S*,4R*,5R*)-1-benzyloxycarbonyl-3-[N-(t-butoxycarbonyl)amino]-4-hydroxymethyl-5-methyl-2-phenylpyrrolidine) as white powders. mp 147-148 C.; IRmax (nujol): 3310(s), 1728(s), 1701(s, shoulder), 1690(vs), 1537(s), 1535(s), 1280(m), 1165(m), 750(m), 700(s) cm-1 ; 1H-NMR δ: 7.52-7.15(m, 9H), 7.05(br.s, 1H), 5.28(br.d, J=8.1 Hz, 1H), 5.05(br.s, 2H), 4.60(ddd, J=11.7, 8.8, 8.1 Hz, 1H), 4.35-4.17(m, 1H), 4.02(br.d, J=8.8 Hz, 1H), 3.71(s, 3H), 2.58(dd, J=11.7, 9.9 Hz, 1H), 1.62(br.d, J=5.5 Hz, 3H), 1.39(s, 9H) ppm.

Workup

  1. temperatureice-cooled
  2. stirringThe reaction mixture was stirred at room temperature for 2 hours, during which the color
  3. filtrationThe mixture was filtered through a pad of Celite
  4. washthe filter cake was washed with CH2Cl2
  5. concentrationThe combined filtrate and washings were concentrated in vacuo
  6. additionThe syrupy residue was diluted with AcOEt--PhMe (2:1, 120 ml)
  7. washwashed with sat. Na2S2O3 aq. solution (×2), sat. NaHCO3 aq. solution (×1), and sat. NaCl aq. solution
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0cd2b77cc00e4ab194af6b992fad5d68
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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