Trifluoroacetic acid → [(2S,3S)-2-amino-3-hydroxy-hexyl]-(2,4-dimethyl-benzyl)-carbamic acid benzyl ester

HRID 1766836Notes

Reaction equation

HRID 1766836 reaction equation
C(OC(=O)[NH:7][C@@H:8]([CH2:14][N:15]([C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[CH3:24])[C@@H:9]([OH:13])[CH2:10][CH2:11][CH3:12])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:28]([O:27][C:25](=[O:26])[N:15]([CH2:14][C@H:8]([NH2:7])[C@@H:9]([OH:13])[CH2:10][CH2:11][CH3:12])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[CH3:24])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69287833(1S,2S)-(1-([benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentyl)-carbamic acid tert-butyl ester

Product 1

HCID 68615332[(2S,3S)-2-amino-3-hydroxy-hexyl]-(2,4-dimethyl-benzyl)-carbamic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The compound (1S,2S)-(1-{[benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentyl)-carbamic acid tert-butyl ester (580 mg, 1.2 mmol, see procedure 12a) was dissolved in CH2Cl2 (9 mL) and treated with TFA (3 mL). The solution was stirred for 3 h and then concentrated in vacuo. The residue was dissolved in benzene and concentrated in vacuo; this procedure was repeated to provide [(2S,3S)-2-amino-3-hydroxy-hexyl]-(2,4-dimethyl-benzyl)-carbamic acid benzyl ester. The amine was dissolved in 12 mL of 2:1 CH2Cl2/DMF. The resultant solution was charged sequentially with mono-benzyl malonate (232 mg, 1.2 mmol), N,N-diisopropylethylamine (1.05 mL, 6.0 mmol) and HATU (547 mg, 1.4 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to provide N-[(1S,2S)-(1-{([benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentyl)]-malonamic acid benzyl ester (517 mg, 77% yield). MS found: (M+Na)+=583.4.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in benzene
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a874a62629964d6d907db3c4ccc82658
Source dataset
uspto-grants-2007_06
Patent number
US07230133B2

Reaction notes

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