Cesium fluoride → (R)-3-{4-[1-(4-CyclohexylphenYl)-3-(3-hydroxymethyl-4-trifluoromethoxyphenyl)ureidomethyl]-benzoylamino}-2-hydroxypropionic acid

HRID 412469Notes

Reaction equation

HRID 412469 reaction equation
[Si]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([NH:21][C:22](=[O:52])[N:23]([CH2:36][C:37]2[CH:51]=[CH:50][C:40]([C:41]([NH:43][CH2:44][C@@H:45]([OH:49])[C:46]([OH:48])=[O:47])=[O:42])=[CH:39][CH:38]=2)C2C=CC(C3CCCCC3)=CC=2)[CH:13]=[CH:14][C:15]=1[O:16][C:17]([F:20])([F:19])[F:18])(C(C)(C)C)(C)C.[F-].[Cs+].[C:55](#N)[CH3:56].O>>[CH:10]1([C:56]2[CH:55]=[CH:39][C:38]([CH:36]([NH:23][C:22]([NH:21][C:12]3[CH:13]=[CH:14][C:15]([O:16][C:17]([F:20])([F:19])[F:18])=[C:10]([CH2:9][OH:8])[CH:11]=3)=[O:52])[C:37]3[CH:51]=[CH:50][C:40]([C:41]([NH:43][CH2:44][C@@H:45]([OH:49])[C:46]([OH:48])=[O:47])=[O:42])=[CH:39][CH:38]=3)=[CH:37][CH:36]=2)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1

Participants

4

Reactant 3

HCID 25953Cesium fluoride2×HCID 18373917Acetonitrile--water (1/1)HCID 67483177(R)-3-{4-[3-[3-(tert-Butyldimethylsilanyloxymethyl)-4-trifluoromethoxyphenyl]-1-(4-cyclohexyl-phenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid

Product 1

HCID 67484637(R)-3-{4-[1-(4-CyclohexylphenYl)-3-(3-hydroxymethyl-4-trifluoromethoxyphenyl)ureidomethyl]-benzoylamino}-2-hydroxypropionic acid

Conditions

Temperature
80 °C

Procedure

(R)-3-{4-[3-[3-(tert-Butyldimethylsilanyloxymethyl)-4-trifluoromethoxyphenyl]-1-(4-cyclohexyl-phenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid (17 mg, 0.023 mmol) was dissolved in acetonitrile:water (9:1) (2 mL) and caesium fluoride (35 mg, 0.35 mmol) added. The reaction mixture was stirred at 80° C. for 6 hours and additional amounts of caesium fluoride (35 mg) added. The mixture was stirred at 60° C. overnight, concentrated in vacuo and diluted with ethyl acetate (10 mL) and water (5 mL). The organic phase was washed with water (3×5 mL) and dried with magnesium sulphate and concentrated in vacua. The residue was purified by preparative HPLC affording the title compound.

Workup

  1. stirringThe mixture was stirred at 60° C. overnight
  2. concentrationconcentrated in vacuo
  3. additiondiluted with ethyl acetate (10 mL) and water (5 mL)
  4. washThe organic phase was washed with water (3×5 mL)
  5. dry with materialdried with magnesium sulphate
  6. concentrationconcentrated in vacua
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-be1626b5ec804b05b7a4499365508abb
Source dataset
uspto-grants-2003_05
Patent number
US06562807B2

Reaction notes

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