Bromocyclopentane → HCID 66932504, compound

HRID 518226Notes

Reaction equation

HRID 518226 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:17](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]1(Br)[CH2:40]C[CH2:38][CH2:37]1>C(#N)C>[CH:17]1([N:14]2[CH2:15][CH2:16][C:11]3([CH2:10][C:9](=[O:28])[C:8]4[C:25](=[CH:26][CH:27]=[C:6](/[CH:5]=[CH:4]/[C:3]([OH:2])=[O:29])[CH:7]=4)[O:24]3)[CH2:12][CH2:13]2)[CH2:38][CH2:37][CH2:36][CH2:40]1

Participants

5

Reactant 3

HCID 8728BromocyclopentaneHCID 11430Potassium CarbonateHCID 52952087(E)-3-{1'-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid methyl ester2×

Product 1

HCID 66932504HCID 66932504, compoundYield 95.1%

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 cyclopentyl bromide (882 mg, 5.92 mmol) were subsequently added and the mixture was heated at 75° C. for 14 h. The solvent was then evaporated and the residue was diluted with water and extracted with ethyl acetate, which was dried and evaporated. The crude orange solid (540 mg) was hydrolyzed as described in Example 55, Step B, giving (E)-3-{1′-cyclopentyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (500 mg) as a light brown solid. The 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′-cyclopentyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as an orange solid (360 mg). The protected hydroxamic acid was dissolved in DCM (4 ml) and treated with 1 M HCl in diethyl ether (4 ml, 4 mmol) as described in Example 2, Step D, giving a light pink solid (247 mg, trifluoroacetate salt) after purification by preparative HPLC.

Workup

  1. customThe solvent was then evaporated
  2. additionthe residue was diluted with water
  3. extractionextracted with ethyl acetate, which
  4. customwas dried
  5. customevaporated

Sources & evidence

ORD record
ord-b8476c75d1054a788ea3518d17c3e06d
Source dataset
uspto-grants-2015_08
Patent number
US09115148B2

Reaction notes

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