Lithium hydroxide, monohydrate → 5-(4-tert-butoxycarbonyl-[1,4]diazepane-1-carbonyl)-1-isopropyl-1H-indole-2-carboxylic acid

HRID 1992492Notes

Reaction equation

HRID 1992492 reaction equation
C([O:3][C:4]([C:6]1[N:7]([CH:31]([CH3:33])[CH3:32])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]([N:17]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19][CH2:18]1)=[O:16])=[CH:10][CH:9]=2)=[O:5])C.O.[OH-].[Li+]>O1CCCC1.CO.O>[C:27]([O:26][C:24]([N:20]1[CH2:21][CH2:22][CH2:23][N:17]([C:15]([C:11]2[CH:12]=[C:13]3[C:8](=[CH:9][CH:10]=2)[N:7]([CH:31]([CH3:32])[CH3:33])[C:6]([C:4]([OH:5])=[O:3])=[CH:14]3)=[O:16])[CH2:18][CH2:19]1)=[O:25])([CH3:28])([CH3:30])[CH3:29]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 685367535-(4-tert-Butoxycarbonyl-[1,4]diazepane-1-carbonyl)-1-isopropyl-1H-indole-2-carboxylic acid ethyl ester

Product 1

HCID 685382125-(4-tert-butoxycarbonyl-[1,4]diazepane-1-carbonyl)-1-isopropyl-1H-indole-2-carboxylic acidYield 42.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(4-tert-butoxycarbonyl-[1,4]diazepane-1-carbonyl)-1-isopropyl-1H-indole-2-carboxylic acid ethyl ester (1.60 g, 3.5 mmol) in tetrahydrofuran (10 ml), methanol (10 ml) and water (2 ml) was added lithium hydroxide monohydrate (2 eq., 168 mg). The mixture was stirred two days at room temperature. The solvent was removed under vacuum and the residue was quenched with 1M aq. dihydrogen potassium phosphate solution to pH 5. The aqueous phase was extracted with ethyl acetate (2×) and the combined organic phases washed with brine, dried over MgSO4 and filtered. The crude product was purified by column chromatography on silica gel (3:1 heptane/ethyl acetate eluant) to afford the product as an off-white powder (644 mg, 42%). MS (m/z): 430.3 (M+H)+.

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue was quenched with 1M aq. dihydrogen potassium phosphate solution to pH 5
  3. extractionThe aqueous phase was extracted with ethyl acetate (2×)
  4. washthe combined organic phases washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customThe crude product was purified by column chromatography on silica gel (3:1 heptane/ethyl acetate eluant)

Sources & evidence

ORD record
ord-ed425f2b6abc456e981643096689516c
Source dataset
uspto-grants-2010_01
Patent number
US07648979B2

Reaction notes

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