Hydrochloric Acid → HCID 22676746, compound

HRID 1006286Notes

Reaction equation

HRID 1006286 reaction equation
O.CC(C)([O-])C.[K+].[CH:8]1([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([O:28][CH2:29][CH3:30])[CH:26]=4)[N:21]([CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=4)[C:20]=3[C:40]([O:42]CC)=[O:41])=[CH:15][CH:14]=2)[CH2:10][CH2:9]1.Cl>C(OCC)C.C(OCC)(=O)C>[CH:8]1([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([O:28][CH2:29][CH3:30])[CH:26]=4)[N:21]([CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=4)[C:20]=3[C:40]([OH:42])=[O:41])=[CH:15][CH:14]=2)[CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 22676833HCID 22676833, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 22676746HCID 22676746, compoundYield 14.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Water (5 uL) was added to a cooled (0° C.) and stirred suspension of potassium t-butoxide (90 mg, 0.80 mmol) in ethyl ether (5 mL). The slurry was stirred for 5 min and then a solution of ethyl 3-[4-(cyclopropylmethoxy)phenyl]-5-ethoxy-1-(3-methoxybenzyl)-1H-indole-2-carboxylate (Example 144, 52 mg, 0.10 mmoL) in ethyl ether (2+1 mL rinse) was added. The mixture was warmed to rt and stirred for 16 h. The solution was adjusted to pH=7 with 1 M hydrochloric acid and diluted with ethyl acetate (50 mL). This mixture was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by preparative TLC, using 1:1 ethyl acetate/hexane as the eluent, to afford 7.0 mg (14%) of desired product. The product had: 1H NMR (300 MHz, acetone-D6) δ 7.45-7.37 (m, 3 H), 7.18 (t, 1 H), 6.99-6.91 (m, 4 H), 6.77 (dd, 1 H), 6.70 (m, 2 H), 5.85 (d, 2 H), 3.99-3.86 (m, 4 H), 3.69 (s, 3 H), 1.36-1.28 (m, 4 H), 0.63-0.59 (m, 2 H), 0.39-0.37 (m, 2 H); mass spectroscopy gave MH+=472.2 (calcd exact mass for C29H29NO5=471.20).

Workup

  1. stirringThe slurry was stirred for 5 min
  2. temperatureThe mixture was warmed to rt
  3. stirringstirred for 16 h
  4. washThis mixture was washed with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-f89f6efb9d314f8186a41972cd2050c0
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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