Dicyclohexylcarbodiimide → HCID 86716159, compound

HRID 1774450Notes

Reaction equation

HRID 1774450 reaction equation
[OH:1][C@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@:3]1([CH2:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)[C:11]1[CH2:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2.C1CCC(N=C=NC2CCCCC2)CC1.C1C2C(COC([NH:62][CH2:63][C:64](O)=[O:65])=O)C3C(=CC=CC=3)C=2C=CC=1>CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[NH2:62][CH2:63][C:64]([O:1][C@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@:3]1([CH2:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)[C:11]1[CH2:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:65]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 93124Fmoc-Gly-OHHCID 60155116HCID 60155116, compound

Product 1

HCID 86716159HCID 86716159, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(((1R,2R)-1-hydroxy-2,3-dihydro-1H,1′H-[2,2′-biinden]-2-yl)methyl)benzoic acid (220 mg, 0.57 mmol), DCC (142 mg, 0.69 mmol) and DMAP (7 mg, 0.059 mmol) in ethyl acetate (10 mL), was added N-[(9H-fluoren-9-ylmethoxy)carbonyl]glycine (171 mg, 0.57 mmol) and then stirred at room temperature for 12 h. The solids were filtered, washed with ethyl acetate (25 ml) and the combined filtrate was washed with 1.5 N HCl (25 mL), water (25 mL), brine (10 mL), dried over anhydrous Na2SO4. The organic layer was evaporated under reduced pressure and the residue 1 (250 mg) was dissolved in dry THF (8 mL) and cooled to 0° C. Dimethylamine (8 mL, 20% in THF) was added drop wise at N2 atmosphere and the reaction mixture was slowly allowed to stir at room temperature for 1 h. The reaction mixture was evaporated under reduced pressure and the residue was purified by CombiFlash using 10% methanol in chloroform as an eluent to yield 130 mg (56%) of the title compound as an off white solid.

Workup

  1. filtrationThe solids were filtered
  2. washwashed with ethyl acetate (25 ml)
  3. washthe combined filtrate was washed with 1.5 N HCl (25 mL), water (25 mL), brine (10 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. customThe organic layer was evaporated under reduced pressure
  6. dissolutionthe residue 1 (250 mg) was dissolved in dry THF (8 mL)
  7. temperaturecooled to 0° C
  8. additionDimethylamine (8 mL, 20% in THF) was added drop wise at N2 atmosphere
  9. stirringto stir at room temperature for 1 h
  10. customThe reaction mixture was evaporated under reduced pressure
  11. customthe residue was purified by CombiFlash

Sources & evidence

ORD record
ord-bc9aae82b67b47b5a4fcc7fc21ed9d3c
Source dataset
uspto-grants-2016_02
Patent number
US09260376B2

Reaction notes

Loading…