Diisopropylethylamine → N-[(1S, 2S)-1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-malonamic acid benzyl ester

HRID 1766838Notes

Reaction equation

HRID 1766838 reaction equation
[CH2:1]([O:8][C:9](=[O:19])[NH:10][CH2:11][C@H:12]([NH2:18])[C@@H:13]([OH:17])[C:14]#[C:15][CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)(=[O:25])[CH2:21][C:22]([O-])=[O:23].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[CH2:27]([O:26][C:20](=[O:25])[CH2:21][C:22]([NH:18][C@@H:12]([CH2:11][NH:10][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:19])[C@@H:13]([OH:17])[C:14]#[C:15][CH3:16])=[O:23])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22247814Benzyl malonateHCID 69196343(2S,3S)-2-amino-3-hydroxy-hex-4-ynyl-carbamic acid benzyl ester

Product 1

HCID 69287828N-[(1S, 2S)-1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-malonamic acid benzyl esterYield 91%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

The compound [(2S,3S)-2-amino-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester (1.45 g, 3.8 mmol, prepared as described in WO PCT 0250019) was dissolved in 38 mL of 1:1 CH2Cl2/DMF. The resultant solution was charged sequentially with mono-benzyl malonate (745 mg, 3.8 mmol), N,N-diisopropylethylamine (6.7 mL, 38 mmol) and HATU (1.75 g, 4.6 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-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-malonamic acid benzyl ester (1.5 g, 91% yield). MS found: (M+H)+=439.4. The entirity of this material was dissolved in THF (18 mL). This solution was charged sequentially with MeOH (6 mL) and aq. LiOH (84 mg LiOH in 6 mL water) and stirred for 12 h at RT. The mixture was concentrated in vacuo, and the residue was lyopholized from 1:1 acetonitrile/water to provide the lithium salt of N-[(1S,2S)-1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-malonamic acid. MS found: (M+H)+=355.3.

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between EtOAc and sat. NH4Cl
  3. extractionThe aqueous phase was extracted with EtOAc (1×)
  4. washThe combined organic extracts were washed with sat. NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-b985c50d1e4d4a4da59c2cce0a747a70
Source dataset
uspto-grants-2007_06
Patent number
US07230133B2

Reaction notes

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