Chloromethyl pivalate → HCID 16042137, compound

HRID 545177Notes

Reaction equation

HRID 545177 reaction equation
[Na].[CH3:2][O:3][C:4]1[C:13]2[C:8](=[C:9]([O:14][CH3:15])[CH:10]=[CH:11][CH:12]=2)[N:7]=[C:6]([C:16]([N:18]2[CH2:23][CH2:22][C:21]3([CH2:32][C:31](=[O:33])[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:34]5[NH:38][N:37]=[N:36][N:35]=5)[CH:29]=4)[O:24]3)[CH2:20][CH2:19]2)=[O:17])[CH:5]=1.[C:39]([O:45][CH2:46]Cl)(=[O:44])[C:40]([CH3:43])([CH3:42])[CH3:41]>CN(C=O)C.C(OCC)(=O)C>[C:39]([O:45][CH2:46][N:36]1[N:37]=[N:38][C:34]([C:28]2[CH:29]=[C:30]3[C:25](=[CH:26][CH:27]=2)[O:24][C:21]2([CH2:22][CH2:23][N:18]([C:16]([C:6]4[CH:5]=[C:4]([O:3][CH3:2])[C:13]5[C:8](=[C:9]([O:14][CH3:15])[CH:10]=[CH:11][CH:12]=5)[N:7]=4)=[O:17])[CH2:19][CH2:20]2)[CH2:32][C:31]3=[O:33])=[N:35]1)(=[O:44])[C:40]([CH3:43])([CH3:42])[CH3:41]

Participants

5

Reactant 2

HCID 87885Chloromethyl pivalateHCID 178492643HCID 178492643, compound

Product 1

HCID 16042137HCID 16042137, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of the sodium salt (105 mg) obtained in Example 18 in 1.0 mL of DMF, was added pivaloyloxymethyl chloride (35.6 μl), and the mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with 20 mL of ethyl acetate, washed with water (4 times) and aqueous saturated sodium chloride solution, then dried over sodium sulfate, and concentrated. The residue was purified through silica gel column chromatography (0.7% methanol/chloroform) to obtain the 2-isomer and 1-isomer. 2-Isomer (major product): 1H-NMR (CDCl3) δ: 8.69 (1H, d, J=2.4 Hz), 8.32 (1H, dd, J=2.4, 8.8 Hz), 7.77 (1H, dd, J=1.0, 8.3 Hz), 7.47 (1H, dd, J=7.7, 8.3 Hz), 7.20 (1H, s), 7.16 (1H, d, J=8.8 Hz), 7.08 (1H, d, J=7.7 Hz), 6.50 (2H, s), 4.64-4.56 (1H, m), 4.24-4.17 (1H, m), 4.08 (3H, s), 4.03 (3H, s), 3.68-3.59 (1H, m), 3.40 (1H, td, J=12.9, 2.8 Hz), 2.88 (1H, d, J=16.6 Hz), 2.81 (1H, d, J=16.6 Hz), 2.28-2.20 (1H, m), 2.14-2.07 (1H, m), 2.01-1.88 (2H, m), 1.23 (9H, s). MS [M+H]+=615. 1-Isomer (minor product): 1H-NMR (CDCl3) δ: 8.30 (1H, d, J=2.4 Hz), 8.09 (1H, dd, J=8.8, 2.4 Hz), 7.78 (1H, dd, J=8.2, 1.0 Hz), 7.48 (1H, t, J=8.2 Hz), 7.25 (1H, d, J=8.2 Hz), 7.20 (1H, s), 7.08 (1H, d, J=8.8 Hz), 6.32 (1H, d, J=11.2 Hz), 6.29 (1H, d, J=11.2 Hz), 4.65-4.57 (1H, m), 4.28-4.20 (1H, m), 4.09 (3H, s), 4.04 (3H, s), 3.69-3.59 (1H, m), 3.40 (1H, td, J=12.8, 2.9 Hz), 2.90 (1H, d, J=16.6 Hz), 2.84 (1H, d, J=16.6 Hz), 2.28-2.21 (1H, m), 2.14-2.07 (1H, m), 2.06-1.89 (2H, m), 1.28 (9H, s). MS [M+H]+=615.

Workup

  1. washwashed with water (4 times) and aqueous saturated sodium chloride solution
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified through silica gel column chromatography (0.7% methanol/chloroform)
  5. customto obtain the 2-isomer and 1-isomer

Sources & evidence

ORD record
ord-3de2659801604ab4b5326411d5336c9d
Source dataset
uspto-grants-2011_05
Patent number
US07935712B2

Reaction notes

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