Methyl chloroformate → HCID 86711212, compound

HRID 1850797Notes

Reaction equation

HRID 1850797 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:19][CH2:18][N:17]([C:20]3[O:24][N:23]=[C:22]([CH:25]([CH3:27])[CH3:26])[N:21]=3)[CH2:16][CH2:15]2)[CH:5]=[CH:4][C:3]=1[CH2:28][C:29](O)=[O:30].ClC(OC)=O.O.[NH2:38][NH2:39]>C1COCC1.CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:15][CH2:16][N:17]([C:20]3[O:24][N:23]=[C:22]([CH:25]([CH3:26])[CH3:27])[N:21]=3)[CH2:18][CH2:19]2)[CH:5]=[CH:4][C:3]=1[CH2:28][C:29]([NH:38][NH2:39])=[O:30]

Participants

7

Reactant 3

HCID 6586Methyl chloroformateHCID 24654Hydrazine hydrate (1:1)HCID 86711213HCID 86711213, compound

Product 1

HCID 86711212HCID 86711212, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution [2-fluoro-4-(2-{(1S,2R)-2-[1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl]cyclopropyl}ethoxy)phenyl]acetic acid (500 mg, 1.152 mmol) in 5 mL of THF cooled to −10° C. via dry ice/methanol bath was added TEA (0.177 mL, 1.268 mmol) followed by methyl chloroformate (0.098 mL, 1.268 mmol) and the resulting mixture stirred for 30 minutes at −10° C. (Precipitate formed after 1 minute of stirring). Filter off the precipitate and wash the solids with 10 mL THF. The filtrate was concentrated under reduced pressure and the residue was used as is for the next reaction sequence. To a solution of this mixed anhydride (265 mg, 0.539 mmol) in 1 mL DMF was added hydrazine monohydrate (0.052 mL, 1.077 mmol) and the resulting mixture stirred overnight at room temperature. The mixture was diluted with ethyl acetate (3 mL) and washed with water (2 mL) followed by brine (2 mL). The organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified via preparative TLC plate (1000 μM, silica gel) developing with 5% methanol in DCM. The band containing the product was washed with 10% methanol in DCM to elute off the product. The solution was concentrated under reduced pressure to afford the product as a white solid. HPLC/MS; 1.35 min (2 minute run), 446 (M+H)+.

Workup

  1. custom(Precipitate formed after 1 minute of stirring)
  2. filtrationFilter off the precipitate
  3. washwash the solids with 10 mL THF
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. stirringthe resulting mixture stirred overnight at room temperature
  6. washwashed with water (2 mL)
  7. dry with materialThe organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified via preparative TLC plate (1000 μM, silica gel)
  11. additionThe band containing the product
  12. washwas washed with 10% methanol in DCM
  13. washto elute off the product
  14. concentrationThe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-1d4292a6d6bf4f9db5294c5fe21397df
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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