Chlorotrimethylsilane → HCID 67253499, compound

HRID 1798154Notes

Reaction equation

HRID 1798154 reaction equation
C[Si](Cl)(C)C.Br[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:13]([O:20][C:21]1[CH:22]=[C:23]([CH:43]=[CH:44][CH:45]=1)[O:24][C:25]1[CH:32]=[C:31]([B:33]2[O:37]C(C)(C)[C:35](C)(C)[O:34]2)[C:28](C=O)=[C:27]([CH3:42])[CH:26]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1.[Zn]>[CH2:11]([O:10][C:8](=[O:9])[CH2:7][CH:35]1[O:34][B:33]([OH:37])[C:31]2[CH:32]=[C:25]([O:24][C:23]3[CH:43]=[CH:44][CH:45]=[C:21]([O:20][CH2:13][C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:22]=3)[CH:26]=[C:27]([CH3:42])[C:28]1=2)[CH3:12]

Participants

6

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 7748Ethyl bromoacetateHCID 86653980HCID 86653980, compound

Product 1

HCID 67253499HCID 67253499, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

To a suspension of zinc dust (1.03 g, 15.75 mmol) in THF (15 mL) was added trimethylsilyl chloride (1.2 mL, 9.45 mmol) at 40° C. The mixture was heated to 55° C. and stirred for 15 minutes. After cooling down to 37° C., ethyl bromoacetate (1.74 mL, 15.75 mmol) was slowly added to the reaction mixture at 37-40° C. After addition, the resulting mixture was cooled to room temperature over 30 minutes. This solution was added to a solution of 4-(3-benzyloxy-phenoxy)-2-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (1.4 g, 3.75 mmol) in THF (50 mL) at −78° C. The mixture was allowed to warm to room temperature over 3 hours, quenched with saturated NH4Cl (10 mL) and extracted 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 (hexane:EtOAc 50:50) to give [6-(3-benzyloxy-phenoxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (0.93 g, 68%). 1H NMR (400 MHz, DMSO): δ 9.22 (s, 1H), 7.41-7.24 (m, 6H), 7.07 (s, 1H), 6.95 (s, 1H), 6.77 (d, J=8.0 Hz, 1H), 6.61 (s, 1H), 6.51 (d, J=6.8 Hz, 1H), 5.48 (d, J=7.2 Hz, 1H), 5.05 (s, 2H), 4.02 (q, J=7.2 Hz, 2H), 3.10 (dd, J=2.4, 15.6 Hz, 1H), 2.30-2.27 (m, 1H), 2.26 (s, 3H), 1.11 (t, J=6.8 Hz, 3H). MS (ESI) m/z=433 [M+H]+.

Workup

  1. temperatureAfter cooling down to 37° C.
  2. additionAfter addition
  3. temperaturethe resulting mixture was cooled to room temperature over 30 minutes
  4. temperatureto warm to room temperature over 3 hours
  5. customquenched with saturated NH4Cl (10 mL)
  6. extractionextracted with EtOAc (2×25 mL)
  7. washThe organic extracts were washed with brine
  8. customdried
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel flash column chromatography (hexane:EtOAc 50:50)

Sources & evidence

ORD record
ord-27575fd35af1474eacdcafd9331fb388
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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