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

HRID 14318

Reaction equation

HRID 14318 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-10591fa1d71f44a894785a2384b0fe13
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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