Acetyl chloride → HCID 57968771, compound

HRID 1255755Notes

Reaction equation

HRID 1255755 reaction equation
NC[C:3]1[CH:19]=[CH:18][C:6]([O:7][C:8]2[CH:17]=[CH:16][C:11]3[B:12]([OH:15])[O:13][CH2:14][C:10]=3[CH:9]=2)=[CH:5][CH:4]=1.[CH3:20][CH2:21][N:22](CC)CC.C(Cl)(=[O:29])C>C(Cl)Cl>[OH:15][B:12]1[C:11]2[CH:16]=[CH:17][C:8]([O:7][C:6]3[CH:5]=[CH:4][C:3]([NH:22][C:21](=[O:29])[CH3:20])=[CH:19][CH:18]=3)=[CH:9][C:10]=2[CH2:14][O:13]1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 57968923Crisaborole intermediate

Product 1

HCID 57968771HCID 57968771, compoundYield 94.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 20 mL scintillation vial containing 5-(4-aminomethyl-phenoxy)-3H-benzo[c][1,2]oxaborol-1-ol (150 mg, 0.59 mmol, 1.0 eq.) in DCM (5.0 mL) was added Et3N (180 μL, 1.3 mmol, 2.2 eq.), followed by acetyl chloride (84 μL, 1.2 mmol, 2.0 eq.). The mixture was stirred at room temperature overnight. The mixture was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with MeOH/DCM (0:100 to 10:90) to give N-[4-(1-hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-phenyl]-acetamide as a white solid. LCMS (m/z) 298 (M+H); 1H NMR (CHLOROFORM-d) δ: 7.55 (d, J=8.0 Hz, 1H), 7.11 (d, J=8.6 Hz, 2H), 6.74-6.83 (m, 3H), 6.68 (d, J=1.4 Hz, 1H), 4.79 (s, 2H), 4.21 (d, J=5.8 Hz, 2H), 1.84 (s, 3H). Amount obtained, 165 mg, 94.3% yield.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. washeluting with MeOH/DCM (0:100 to 10:90)

Sources & evidence

ORD record
ord-501bcaf4b77b477b9c73743f4d3816eb
Source dataset
uspto-grants-2013_06
Patent number
US08461135B2

Reaction notes

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