Hydrochloric Acid → 3-Chloro-5-(dihydroxyboryl)-1-(4-isopropoxyphenyl)indole-2-carboxylic acid ethyl ester

HRID 646138Notes

Reaction equation

HRID 646138 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH:24]([CH3:26])[CH3:25])=[CH:19][CH:18]=2)[C:8]2[C:13]([C:14]=1[Cl:15])=[CH:12][C:11](I)=[CH:10][CH:9]=2)=[O:5])[CH3:2].C([Mg]Cl)(C)C.[Li+].[Cl-].[B:34](OCC)([O:38]CC)[O:35]CC.Cl>C1COCC1.[Cl-].[Na+].O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH:24]([CH3:26])[CH3:25])=[CH:19][CH:18]=2)[C:8]2[C:13]([C:14]=1[Cl:15])=[CH:12][C:11]([B:34]([OH:38])[OH:35])=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 9009Triethyl borateHCID 433294Lithium ChlorideHCID 686997713-Chloro-5-iodo-1-(4-isopropoxyphenyl)indole-2-carboxylic acid ethyl esterHCID 178418918HCID 178418918, compound

Product 1

HCID 686978453-Chloro-5-(dihydroxyboryl)-1-(4-isopropoxyphenyl)indole-2-carboxylic acid ethyl esterYield 86.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-40 °C

Procedure

To solution of 3-chloro-5-iodo-1-(4-isopropoxyphenyl)-1H-indole-2-carboxylic acid ethyl ester (1.45 g, 3.0 mmol, see step (a) above) in THF (9 mL) was added i-PrMgCl×LiCl (0.95 M solution in THF; 3.26 mL, 3.1 mmol) at −40° C. over 5 min. After stirring for 15 min at −40° C., B(OEt)3 (1.56 mL, 9.0 mmol) was added. The temperature of the reaction mixture was allowed to reach 0° C. over 2 h, then HCl (2.5 M solution in water; 3.6 mL, 36 mmol) was added and stirring continued for a further 1 h at 0° C. The reaction mixture was diluted with brine (70 mL) and extracted with t-BuOMe (4×70 mL). The combined organic extracts were washed with brine (100 mL), dried over Na2SO4 and concentrated. The solid thereby obtained was washed several times with light petrol and filtered affording pure sub-title compound (1.04 g, 86%)

Workup

  1. waitto reach 0° C. over 2 h
  2. stirringstirring
  3. waitcontinued for a further 1 h at 0° C
  4. extractionextracted with t-BuOMe (4×70 mL)
  5. washThe combined organic extracts were washed with brine (100 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe solid thereby obtained
  9. washwas washed several times with light petrol
  10. filtrationfiltered

Sources & evidence

ORD record
ord-9011f6e8f373477593836f2eee03a1d1
Source dataset
uspto-grants-2010_04
Patent number
US07705023B2

Reaction notes

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