Tetrahydrofuran → HCID 18363234, compound

HRID 381773Notes

Reaction equation

HRID 381773 reaction equation
C[Mg]Br.[Cl:4][C:5]1[C:14]([C:15]2[N:16]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:17]3[C:22]([CH:23]=2)=[CH:21][C:20](C=O)=[CH:19][CH:18]=3)=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]=1.C1C[O:36][CH2:35][CH2:34]1>>[Cl:4][C:5]1[C:14]([C:15]2[N:16]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:17]3[C:22]([CH:23]=2)=[CH:21][C:20]([CH2:34][CH2:35][OH:36])=[CH:19][CH:18]=3)=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 22668284HCID 22668284, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 18363234HCID 18363234, compound

Procedure

A solution of methylmagnesium bromide in THF (3 M, 0.85 mL, 2.56 mmol, 1.3 equiv) was added to a solution of 2-(2-chloro-3-quinolinyl)-5-formyl-1H-indole-1-carboxylate (8-1, 800 mg, 2.0 mmol, 1 equiv) in THF (25 mL) at 0° C., and the resulting mixture was stirred for 30 minutes. The reaction mixture was partitioned between pH 7 phosphate buffer solution and ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (100% hexane, grading to 70% EtOAc in hexane) to provide tert-butyl 2-(2-chloro-3-quinolinyl)-5-(1-hydroxyethyl)-1H-indole-1-carboxylate (8-2) as a white foam. 1H NMR (500 MHz, CDCl3) δ8.29 (d, 1H, J=8.8 Hz), 8.18 (s, 1H), 8.08 (d, 1H, J=8.5 Hz), 7.87 (d, 1H, J=7.8 Hz), 7.78 (br t, 1H, J=7.1 Hz), 7.64 (s, 1H), 7.61 (br t, 1H, J=7.1 Hz), 7.42 (dd, 1H, J=8.6, 1.5 Hz), 6.66 (s, 1H), 5.05 (m, 1H), 1.58 (d, 3H, J=6.6 Hz), 1.27 (s, 9H).

Workup

  1. customThe reaction mixture was partitioned between pH 7 phosphate buffer solution and ethyl acetate (2×100 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (100% hexane, grading to 70% EtOAc in hexane)

Sources & evidence

ORD record
ord-ebc15ff1640446d0adb0d06be60196ec
Source dataset
uspto-grants-2001_10
Patent number
US06306874B1

Reaction notes

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