Triethylamine → tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1H-pyrrol-2-ylmethyl)amino]propylcarbamate

HRID 349107Notes

Reaction equation

HRID 349107 reaction equation
[NH2:1][CH2:2][C@@H:3]([OH:22])[C@@H:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]([F:13])[CH:7]=1.[NH:23]1[CH:27]=[CH:26][CH:25]=[C:24]1[CH:28]=O.C(N(CC)CC)C.S([O-])([O-])(=O)=O.[Mg+2].[BH4-].[Na+]>C(Cl)(Cl)Cl.CO>[F:12][C:10]1[CH:11]=[C:6]([CH:7]=[C:8]([F:13])[CH:9]=1)[CH2:5][C@H:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:18])[CH3:20])[C@H:3]([OH:22])[CH2:2][NH:1][CH2:28][C:24]1[NH:23][CH:27]=[CH:26][CH:25]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 13854Pyrrole-2-carboxaldehydeHCID 24083Sulfuric acid magnesium salt (1:1)HCID 4311764Sodium borohydrideHCID 58802335tert-butyl (1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate

Product 1

HCID 86594202tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1H-pyrrol-2-ylmethyl)amino]propylcarbamateYield 62%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A mixture of tert-butyl (1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate (170 mg, 0.538 mmol), 1H-pyrrole-2-carbaldehyde (51 mg, 0.538 mmol), and triethylamine (60 mg, 0.592 mmol) was stirred in chloroform (10 mL) containing magnesium sulfate for 4 h. The reaction mixture was filtered and concentrated under reduced pressure. The resulting residue was dissolved in 2-propanol (10 mL) and sodium borohydride (26 mg, 0.699 mmol) was added. The reaction mixture was stirred overnight and then treated with methanol. The reaction mixture was concentrated under reduced pressure. Purification by flash column chromatography (silica, 9:1 chloroform/methanol) gave tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1H-pyrrol-2-ylmethyl)amino]propylcarbamate (132 mg): 1H NMR (300 MHz, CD3OD) δ 6.82 (m, 4H), 6.21 (s, 1H), 6.09 (m, 1H), 4.09 (s, 2H), 3.66 (m, 2H), 3.19 (m, 1H), 3.13 (m, 1H), 3.03 (m, 1H) 2.88 (m, 1H), 1.31 (s, 9H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe resulting residue was dissolved in 2-propanol (10 mL)
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 9:1 chloroform/methanol)

Sources & evidence

ORD record
ord-fd5b0e3f80774ca9929fc82c5144319d
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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