Methanol → HCID 13131524, compound

HRID 1388685Notes

Reaction equation

HRID 1388685 reaction equation
C([O:3][P:4]([CH3:26])([NH:6][C@H:7]([C:15]([NH:17][C@H:18]([C:23]([OH:25])=[O:24])[CH2:19][CH:20]([CH3:22])[CH3:21])=[O:16])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.Br[Si](C)(C)C.CO>C(Cl)Cl.C(N(CC)CC)C.O>[OH:5][P:4]([CH3:26])([NH:6][C@H:7]([C:15]([NH:17][C@H:18]([C:23]([OH:25])=[O:24])[CH2:19][CH:20]([CH3:22])[CH3:21])=[O:16])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:3]

Participants

8

Reactant 4

HCID 887MethanolHCID 76113BromotrimethylsilaneHCID 11708267BistrimethylsilylacetamidHCID 54451073L-Leucine, N-[N-(ethoxymethylphosphinyl)-L-phenylalanyl]-

Product 1

HCID 13131524HCID 13131524, compoundYield 10.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

N-[N-[Ethoxy(methyl)phosphinyl]-L-phenylalanyl]-L-leucine (0.386 g., 1.0 mmole) is thoroughly dried, and then allowed to dissolve in methylene chloride (5 ml.). The solution is flushed with argon and treated with bis(trimethylsilyl)acetamide (0.33 ml., 1.3 mmole), stirred for two hours at room temperature, then concentrated in vacuo (less than 0.3 mm of Hg) and again taken up in methylene chloride (4 ml.). This solution is treated with bromotrimethylsilane (0.29 ml., 2.2 mmole) under argon, stirred overnight at room temperature, then treated slowly with a mixture of methanol (3.1 ml.), water (0.78 ml.), and triethylamine (0.78 ml.). After again stirring overnight at room temperature, the mixture is concentrated to dryness, taken up in water (approximately 3 ml.), and passed through an AG-50W-2 Li+ column (25 ml. settled bed). Fractions of approximately 8 ml. each are collected and those containing the product (fractions numbered 1 to 4) are pooled and concentrated to a small volume (approximately 2 ml.). This material is applied to a column of HP-20 and eluted with water. Fractions of approximately 8 ml. each are collected and those containing the product (fractions numbered 11 to 19) are pooled and concentrated to approximately 20 ml. and lyophilized to a white powder (0.168 g.). A sample of this powder (0.04 g.) is taken up in water, filtered (millipore) and relyophilized to give an analytical sample (0.039 g.) of N-[N-[hydroxy(methyl)phosphinyl]-L-phenylalanyl]-L-leucine, dilithium salt; m.p. greater than 250° (turns pink at 210°). Tlc (isopropanol/water/con. NH4OH, 7:2:1) single spot Rf is 0.51. [α]D25 =-36.6° (c=1.0, water).

Workup

  1. customThe solution is flushed with argon
  2. concentrationconcentrated in vacuo (less than 0.3 mm of Hg)
  3. stirringstirred overnight at room temperature
  4. stirringAfter again stirring overnight at room temperature
  5. concentrationthe mixture is concentrated to dryness
  6. customeach are collected
  7. concentrationconcentrated to a small volume (approximately 2 ml.)
  8. washeluted with water
  9. customeach are collected
  10. concentrationconcentrated to approximately 20 ml
  11. filtrationfiltered (millipore)

Sources & evidence

ORD record
ord-604999e0fc514b2f8eadb8f525069248
Source dataset
uspto-grants-1984_02
Patent number
US04432972

Reaction notes

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