9-Fluorenylmethyl chloroformate → HCID 131720400, compound

HRID 726797Notes

Reaction equation

HRID 726797 reaction equation
[NH:1]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:2]([C:11]([N:13]1[CH2:25][CH2:24][CH2:23][C@H:14]1[C:15]([NH:17][C@@H:18]([C:20]([NH2:22])=[O:21])[CH3:19])=[O:16])=[O:12])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][CH:8]([CH3:10])[CH3:9].[C:33](Cl)([O:35][CH2:36][CH:37]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:43]2[C:38]1=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:34]>C1COCC1.CCOC(C)=O>[NH:1]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:2]([C:11]([N:13]1[CH2:25][CH2:24][CH2:23][C@H:14]1[C:15]([NH:17][C@@H:18]([C:20]([NH2:22])=[O:21])[CH3:19])=[O:16])=[O:12])[CH2:3][CH2:4][CH2:5][CH2:6][N:7]([C:33]([O:35][CH2:36][CH:37]1[C:38]2[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:44]2[C:49]1=[CH:48][CH:47]=[CH:46][CH:45]=2)=[O:34])[CH:8]([CH3:10])[CH3:9]

Participants

5

Reactant 2

HCID 343679-Fluorenylmethyl chloroformateHCID 131720399HCID 131720399, compound

Product 1

HCID 131720400HCID 131720400, compoundYield 79.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent3×

Procedure

A solution of Boc-Lys(iPr)-Pro-D-Ala-NH2 (9.11 gm) in 10% Na2 CO3 (25 mL) and THF (30 mL) was cooled to 0° C. and treated with a solution of Fmoc-Cl (6.46 gm) in THF. After 1 hour at 0° C. the mixture was partitioned between EtOAc (200 mL) and water (100 mL) and the layers were separated. The organic layer was washed with water (100 mL), 10% citric acid (2×100 mL) and water (100 mL), then dried over Na2SO4 and evaporated to dryness to yield an oil. The residue was dissolved in EtOAc and precipitated from heptane to yield 11.66 gm of crude product. This material was dissolved in a small in EtOAc and loaded onto a silica gel (200 gm) column which was eluted with an EtOAc/heptane mixture (2/1), followed by EtOAc and finally by ethanol. The product-containing fractions were combined and evaporated in vacuo to dryness to yield an oil. The residue was dissolved in a small amount of EtOAc and precipitated from heptane to yield 10.75 gm of Boc-Lys(iPr,Fmoc)-Pro-D-Ala-NH2. HPLC: 98.1%, MS: (M+H)+ =678, (M+NH4)+ =695, [a]D=-12.2 (c=1, HOAc)

Workup

  1. customAfter 1 hour at 0° C. the mixture was partitioned between EtOAc (200 mL) and water (100 mL)
  2. customthe layers were separated
  3. washThe organic layer was washed with water (100 mL), 10% citric acid (2×100 mL) and water (100 mL)
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness
  6. customto yield an oil
  7. customprecipitated from heptane
  8. customto yield 11.66 gm of crude product
  9. washwas eluted with an EtOAc/heptane mixture (2/1)
  10. customevaporated in vacuo to dryness
  11. customto yield an oil
  12. customprecipitated from heptane

Sources & evidence

ORD record
ord-7e1de4e56b404ddc94e2d1c357ac5a47
Source dataset
uspto-grants-1998_01
Patent number
US05710246

Reaction notes

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