Isopropyl iodide → HCID 67286778, compound

HRID 518225Notes

Reaction equation

HRID 518225 reaction equation
C[O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:28].C([O-])([O-])=O.[K+].[K+].[CH:36](I)([CH3:38])[CH3:37]>C(#N)C>[CH:36]([N:14]1[CH2:15][CH2:16][C:11]2([CH2:10][C:9](=[O:28])[C:8]3[C:25](=[CH:26][CH:27]=[C:6](/[CH:5]=[CH:4]/[C:3]([OH:2])=[O:29])[CH:7]=3)[O:24]2)[CH2:12][CH2:13]1)([CH3:38])[CH3:37]

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 52952087(E)-3-{1'-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid methyl ester2×

Product 1

HCID 67286778HCID 67286778, compoundYield 97.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

(E)-3-{4-Oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (500 mg, 1.48 mmol, Intermediate 1, hydrochloride salt) was suspended in acetonitrile (65 ml). K2CO3 (818 mg, 5.92 mmol) and isopropyl iodide (523 mg, 3.07 mmol) were subsequently added and the mixture was heated at 75° C. for 14 h. The solvent was evaporated and the residue was diluted with water and extracted with ethyl acetate. The combined organic phases were dried, evaporated, and the crude oily residue (575 mg) was hydrolyzed as described in Example 55, Step B, giving (E)-3-{1′-isopropyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (475 mg) as an orange solid (hydrochloride salt). The resulting acid was suspended in DCM (16 ml), TEA (0.30 ml) was added, and the resulting clear solution was treated with NH2OTHP following the procedure described in Example 1, Step B, giving (E)-3-{1′-isopropyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as an orange solid (314 mg). The compound was dissolved in DCM (4 ml) and treated with 1 M HCl in diethyl ether (6 ml, 6 mmol) as described in Example 2, Step D, giving a light pink solid (192 mg, trifluoroacetate salt) after purification by preparative HPLC.

Workup

  1. customThe solvent was evaporated
  2. additionthe residue was diluted with water
  3. extractionextracted with ethyl acetate
  4. customThe combined organic phases were dried
  5. customevaporated

Sources & evidence

ORD record
ord-cc358ca6fdf449e693cf7fb47fa15dc5
Source dataset
uspto-grants-2015_08
Patent number
US09115148B2

Reaction notes

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