Chlorotrimethylsilane → [1-Hydroxy-4-methoxymethyl-6-(tetrahydro-pyran-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester

HRID 1798084Notes

Reaction equation

HRID 1798084 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][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[CH:21]=[C:20]([B:31]2[O:35][C:34](C)(C)C(C)(C)[O:32]2)[C:17]=1C=O>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]([O:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)[CH:23]=[C:16]([CH2:15][O:14][CH3:13])[C:17]1=2)[CH3:12]

Participants

6

Reactant 3

HCID 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 58292743[1-Hydroxy-4-methoxymethyl-6-(tetrahydro-pyran-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl esterYield 67%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

A suspension of zinc (8.04 g, 123 mmol) in THF (80 mL) was added TMSCl (2.31 ml, 18.2 mmol) at 40° C. The temperature was increased to 55° C. over 30 min. Then, the temperature was lowered to 37° C. and ethyl 2-bromoacetate (12.6 mL, 114 mmol) was added slowly. The resulting solution was stirred for 30 min and cooled from 45° C. to room temperature and stood by for 1 h. The top clear layer (25 mL) 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 (3.56 g, 9.46 mmol) in THF (50 ml) at −78° C. After the addition, the reaction was warmed to 0° C. using an ice bath and stirred at 0° C. 30 min. The reaction mixture was quenched with aqueous NH4Cl and extracted with ethyl acetate. The organic phase was separated, dried (Na2SO4), and concentrated. The residue was purified by the flash column chromatography (silica, hexanes/ethyl acetate=2:1) to afford the title compound (2.30 g, 67%). 1H NMR (300 MHz, CDCl3) δ 7.33 (s, 1H), 7.11 (s, 1H), 5.73-5.70 (m, 1H), 5.46-5.44 (m, 1H), 4.54-4.39 (m, 2H), 4.21-4.16 (q, 2H), 3.94-3.90 (m, 1H), 3.66-3.60 (m, 1H), 3.38 (s, 3H), 3.18-3.11 (m, 1H), 2.43-2.34 (m, 1H), 1.88-1.85 (m, 2H), 1.70-1.61 (m, 4H), 1.26 (t, 3H).

Workup

  1. customwas lowered to 37° C.
  2. temperaturecooled from 45° C. to room temperature
  3. customstood by for 1 h
  4. additionAfter the addition
  5. temperaturethe reaction was warmed to 0° C.
  6. stirringstirred at 0° C
  7. custom30 min
  8. customThe reaction mixture was quenched with aqueous NH4Cl
  9. extractionextracted with ethyl acetate
  10. customThe organic phase was separated
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated
  13. customThe residue was purified by the flash column chromatography (silica, hexanes/ethyl acetate=2:1)

Sources & evidence

ORD record
ord-c18f245b5b0c422e81fab59276f05d93
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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