Hydrochloric Acid → (1,6-Dihydroxy-4-methoxymethyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester

HRID 1798062Notes

Reaction equation

HRID 1798062 reaction equation
C[Si](Cl)(C)C.Br[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH3:13][O:14][CH2:15][C:16]1[CH:23]=[C:22]([O:24]C2CCCCO2)[CH:21]=[C:20]([B:31]2[O:35][C:34](C)(C)C(C)(C)[O:32]2)[C:17]=1C=O.Cl>C1COCC1.[Zn]>[CH2:11]([O:10][C:8](=[O:9])[CH2:7][CH:34]1[O:35][B:31]([OH:32])[C:20]2[CH:21]=[C:22]([OH:24])[CH:23]=[C:16]([CH2:15][O:14][CH3:13])[C:17]1=2)[CH3:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 7748Ethyl bromoacetateHCID 582928322-Methoxymethyl-4-(tetrahydro-pyran-2-yloxy)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde

Product 1

HCID 58292640(1,6-Dihydroxy-4-methoxymethyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl esterYield 68%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

To a suspension of zinc dust (5.35 g, 82.3 mmol) in THF (10 mL) was added trimethylsilyl chloride (1.1 g, 10.15 mmol) at 40° C. The mixture was heated to 55° C. and stirred for 45 minutes. After cooling down to 37° C., ethyl bromoacetate (7.58 mL, 74.87 mmol) was slowly added to the reaction mixture at 37-40° C. After addition, the resulting mixture was allowed to cool to room temperature over 30 minutes. This solution was added to a solution of 2-methoxymethyl-4-(tetrahydro-pyran-2-yloxy)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (1.99 g, 5.29 mmol) in THF (6 mL) at 0° C. The mixture was stirred for 10 minutes before treating with 3 N HCl and extracting with EtOAc (2×25 mL). The organic extracts were washed with brine, dried and concentrated in vacuo. The residue was purified by silica gel flash column chromatography and lyophilized to give (1,6-dihydroxy-4-methoxymethyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (1.0 g, 68%). 1H NMR (400 MHz, Acetone-d4) δ 8.40 (s, 1H), 8.00 (s, 1H), 7.10 (s, 1H), 6.90 (s, 1H), 5.60 (m, 1H), 4.47 (m, 2H), 4.08 (m, 2H), 3.37 (s, 3H), 3.10 9m, 1H), 2.25 (m, 1H), 1.20 (m, 3H).

Workup

  1. temperatureAfter cooling down to 37° C.
  2. additionAfter addition
  3. temperatureto cool to room temperature over 30 minutes
  4. stirringThe mixture was stirred for 10 minutes
  5. extractionextracting with EtOAc (2×25 mL)
  6. washThe organic extracts were washed with brine
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-b85b4cf70d364ddbae91f72aa8b47ec6
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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