Diethyl Ether → HCID 10888757, compound

HRID 1884404Notes

Reaction equation

HRID 1884404 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH2:10][C:11]([O-:13])=[O:12])=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[CH3:14]N(C)CCCN=C=NCC.CCOCC>CC#N.CN(C1C=CN=CC=1)C>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 86759497HCID 86759497, compound

Product 1

HCID 10888757HCID 10888757, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

Methyl 1-(S-[4-tert-butoxycarbonyl)-4-(tert -butoxycarbonylamino)]butanoyl)indoline-5-acetate 7. Crude 3 (327 mg, 1.9 mmol) was prepared as described above (see compound 4), dissolved in dry MeCN (30 mL) and treated with DMAP (611 mg, 5 mmol) and N-tert-BOC-L-glutamic acid α-tert-butyl ester (607 mg, 2 mmol), followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (422 mg, 2.2 mmol). The mixture was stirred at rt for 18 h, then evaporated and the residue was dissolved in EtOAc and washed successively with 0.5 M aq. HCl, saturated aq. NaHCO3 and brine, dried and evaporated to give a viscous oil. Flash chromatography [EtOAc-hexanes (55:45)] and trituration with ether gave. 6 as white crystals (626 mg, 69%), mp 80-81° C. (EtOAc-hexanes); IR: νmax/cm−1; 3340, 1730, 1680, 1655, 1625; 1H NMR: δH (400 MHz) 8.15 (d, J=8 Hz, 1H), 7.07-7.11 (m, 2H), 5.23 (d, J=6.9 Hz, 1H), 4.22 (m, 1H), 4.03 (2×t, J=8.5 Hz, 2H; rotamers), 3.68 (s, 3H), 3.57 (s, 2H), 3.17 (t, J=8.5 Hz, 2H), 2.43-2.59 (m, 2H), 2.18-2.31 (m, 1H), 1.98-2.07 (m, 1H), 1.47 (s, 9H) and 1.41 (s, 9H). Anal. Calcd for C25H36N2O7: C, 63.01; H, 7.61; N, 5.88. Found: C, 63.08; H, 7.81; N, 5.64.

Workup

  1. customevaporated
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed successively with 0.5 M aq. HCl, saturated aq. NaHCO3 and brine
  4. customdried
  5. customevaporated
  6. customto give a viscous oil

Sources & evidence

ORD record
ord-e2a982368a534d639641839bd68e306a
Source dataset
uspto-grants-2004_07
Patent number
US06765014B1

Reaction notes

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