Hydrochloric Acid → HCID 58292857, compound

HRID 1798156Notes

Reaction equation

HRID 1798156 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([OH:24])[CH:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2].[C:26]([O:30][C:31](=[O:37])[NH:32][CH2:33][CH2:34][CH2:35]Br)([CH3:29])([CH3:28])[CH3:27].[H-].[Na+].[NH4+].[Cl-].Cl>CN(C=O)C.O>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH2:35][CH2:34][CH2:33][NH:32][C:31]([O:30][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:37])[CH:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 58292671HCID 58292671, compound

Product 1

HCID 58292857HCID 58292857, compoundYield 67.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of [1-hydroxy-6-(3-hydroxy-phenoxy)-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (0.53 g, 1.54 mmol) and (3-bromo-propyl)-carbamic acid tert-butyl ester (0.74 g, 3.09 mmol) in DMF (20 mL) at 0° C. was added NaH (0.22 g, 4.64 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 20 hours. Saturated NH4Cl (10 mL) and water (10 mL) were added and the solution acidified to pH˜5 with dilute HCl. The mixture was extracted with EtOAc (2×20 mL) and the organic extracts washed with water (10 mL), dried and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (DCM:MeOH 95:5) to give {6-[3-(3-tert-butoxycarbonylamino-propoxy)-phenoxy]-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl}-acetic acid ethyl ester (0.52 g, 67%). 1H NMR (400 MHz, DMSO): δ 9.18 (s, 1H), 7.24 (t, J=8.0 Hz, 1H), 7.06 (s, 1H), 6.95 (d, J=6.0 Hz, 1H), 6.85 (s, 1H), 6.67 (d, J=8.4 Hz, 1H), 6.51 (d, J=6.0 Hz, 2H), 5.47 (t, J=11.6 Hz, 1H), 4.02 (q, J=7.2 Hz, 2H), 3.93 (t, J=6.0 Hz, 2H), 3.07-3.02 (m, 3H), 2.28-2.27 (m, 1H), 2.26 (s, 3H), 1.77 (t, J=6.4 Hz, 2H), 1.33 (s, 12H), 1.11 (t, J=6.8 Hz, 3H).

Workup

  1. extractionThe mixture was extracted with EtOAc (2×20 mL)
  2. washthe organic extracts washed with water (10 mL)
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel flash column chromatography (DCM:MeOH 95:5)

Sources & evidence

ORD record
ord-d2eb5ea1e4b342deafd4100098f68963
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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