Methanol → 2-(2-Adamantyloxycarbonyl)amino-3-(3-indolyl)butanoic acid

HRID 233631Notes

Reaction equation

HRID 233631 reaction equation
[NH2:1][CH:2]([CH:6]([C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)[CH3:7])[C:3]([OH:5])=[O:4].C(=O)([O-])O.[Na+].Cl[C:23]([O:25][CH:26]1[CH:33]2[CH2:34][CH:29]3[CH2:30][CH:31]([CH2:35][CH:27]1[CH2:28]3)[CH2:32]2)=[O:24].CO>[OH-].[Na+].O1CCOCC1.ClCCl>[CH:33]12[CH2:34][CH:29]3[CH2:30][CH:31]([CH2:35][CH:27]([CH2:28]3)[CH:26]1[O:25][C:23]([NH:1][CH:2]([CH:6]([C:8]1[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=1)[CH3:7])[C:3]([OH:5])=[O:4])=[O:24])[CH2:32]2

Participants

8

Reactant 4

HCID 887MethanolHCID 2921702-Amino-3-(3-indolyl)butanoic acidHCID 516892Sodium BicarbonateHCID 108785372-adamantyl Chloroformate

Product 1

HCID 221022962-(2-Adamantyloxycarbonyl)amino-3-(3-indolyl)butanoic acidYield 63%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Percent amino acid (75) (449 mg, 2.29 mmol) in 1N sodium hydroxide (2.29 mL) was added to sodium hydrogen carbonate (211 mg, 2.5 mmol). This mixture was cooled to 0° C. (ice bath), dioxan. (2.29 mL) was added, followed by dropwise addition with stirring of a solution of the chloroformate (76) (742 mg, 34.46 mmol) in dioxan (2.29 mL). When all the amino acid had gone (TLC SiO2 :4% methanol in dichloromethane), the dioxan was removed in vacuo and the residue partitioned between 10% citric acid and ethyl acetate. The aqueous phase was extracted further with ethyl acetate. The organic extracts were combined, dried (MgSO4), and evaporated to dryness. The crude acid was purified by column chromatography on normal silica [hexane: ethyl acetate (3:20+0.5% acetic acid as eluant] to give 2-(2-adamantyloxycarbonyl)amino-3-(3-indolyl) butanoic acid (77) (570 mg, 63%); δ H (300M Hz, d6 -DMSO), 1.34 (3H, d, J 8Jz. CH3), 1.68-2.00 (14H, m, adamantyl), 3.40-3.53 (1H, m, indCH(CH3)), 4.36 (1H, brt, CH(CO2H)), 4.59 (1H, s, adamantyl 2-H), 6.73 (1H, d, J 9 Hz, urethane NH), 6.96 (1H, t, J 7 Hz, indole 5-H), 7.06 m (1H, t, J 7 Hz, indole 6-H), 7.17 (1H, brs, indole 2-H), 7.33 (1H, d, J 8 Hz, indole 7-H), 7.60 (1H, d, J 8 Hz, indole 4-H), 10.83 (1H, s, indole NH)m, ca 12.6 (vbrs, CO2H).

Workup

  1. addition(2.29 mL) was added
  2. additionfollowed by dropwise addition
  3. customthe dioxan was removed in vacuo
  4. customthe residue partitioned between 10% citric acid and ethyl acetate
  5. extractionThe aqueous phase was extracted further with ethyl acetate
  6. dry with materialdried (MgSO4)
  7. customevaporated to dryness
  8. customThe crude acid was purified by column chromatography on normal silica [hexane: ethyl acetate (3:20+0.5% acetic acid as eluant]

Sources & evidence

ORD record
ord-877e5140f61b45a7b4ef7a9552f7052c
Source dataset
uspto-grants-1997_01
Patent number
US05593967

Reaction notes

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