Cyclohexanol → HCID 16004802, compound

HRID 348450Notes

Reaction equation

HRID 348450 reaction equation
[CH3:1][O:2][C:3](=[O:22])[CH2:4][O:5][C:6]1[N:11]=[CH:10][C:9]([C:12](=[O:21])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[CH:8][N:7]=1.[CH:23]1(O)[CH2:28][CH2:27]C[CH2:25][CH2:24]1.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl.CN(C1C=CN=CC=1)C>[CH:1]1([O:2][C:3](=[O:22])[CH2:4][O:5][C:6]2[N:11]=[CH:10][C:9]([C:12](=[O:21])[NH:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)=[CH:8][N:7]=2)[CH2:27][CH2:28][CH2:23][CH2:24][CH2:25]1

Participants

6

Reactant 3

HCID 7966CyclohexanolHCID 10868DicyclohexylcarbodiimideHCID 69522849[5-(4-Fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid methyl ester

Product 1

HCID 16004802HCID 16004802, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of [5-(4-fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid methyl ester (prepared above, 50 mg, 0.17 mmol) and cyclohexanol (51 mg, 0.51 mmol) were slurried in dichloromethane. DMAP (17 mg, 0.14 mmol) was added, and the slurry became homogeneous and colorless. The solution was then treated with 1 M dicyclohexylcarbodiimide (190 μL, 0.19 mmol), which initiated formation of a white slurry within 5 min. After 1 h, thin layer chromatography indicated complete conversion. The reaction was quenched with 10 mL 1 M HCl(aq) and 25 mL dichloromethane. The phases were partitioned, and the aqueous phase extracted with 5 mL dichloromethane. The organic phases were combined and sequentially washed with 10 mL portions of 0.1 M HCl(aq), saturated. NaHCO3(aq) and brine. The organic layer was dried using Na2SO4, filtered and concentrated. The 101 mg of crude product was chromatographed over SiO2 (1:1 ethyl acetate:hexane) to yield 50 mg (79%) of the titled compound. ESI-MS m/z 374 (MH+), 372 (M−H−).

Workup

  1. customwithin 5 min
  2. customThe reaction was quenched with 10 mL 1 M HCl(aq) and 25 mL dichloromethane
  3. customThe phases were partitioned
  4. extractionthe aqueous phase extracted with 5 mL dichloromethane
  5. washsequentially washed with 10 mL portions of 0.1 M HCl(aq)
  6. customThe organic layer was dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe 101 mg of crude product was chromatographed over SiO2 (1:1 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-d2a24fc3ef774013bf0b5e417a150a47
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Reaction notes

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