HCID 15024522, compound → HCID 15870352, compound

HRID 617709Notes

Reaction equation

HRID 617709 reaction equation
[NH:1]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C@H:2]([C:18]([NH:20][C:21]([C:24]([O:26]C)=[O:25])([CH3:23])[CH3:22])=[O:19])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][CH:5]=1>C1COCC1.O>[NH:1]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C@H:2]([C:18]([NH:20][C:21]([C:24]([OH:26])=[O:25])([CH3:23])[CH3:22])=[O:19])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:9]=1

Participants

3

Reactant 1

HCID 15024522HCID 15024522, compound

Product 1

HCID 15870352HCID 15870352, compoundYield 95.1%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
22 °C

Procedure

A solution containing about 260 mg of compound 7 and 91.5 mg of LiOH monohydrate in 7.5 ml of THF/H2O (2:1) was stirred at 22° C. for about 3 hours. The organic solvent was evaporated and the aqueous solution was extracted with Et2O (2×10 ml) and then acidified to a pH of less than 1 with 1 N HCl. The mixture was extracted again with Et2O (3×10 ml) and the combined organic extracts were dried over Na2SO4 and evaporated to yield about 240 mg of Boc-Tyr(OBn)-Aib-OH. A solution containing about 200 mg of Boc-Tyr(OBn)-Aib-OH in 10 ml of dry CH3CN was treated at 0° C. with 95 mg of DCC and stirred for about 2 hours. After filtration through florosil, the solution was evaporated to dryness. The resulting crude product (8) was dissolved in 2 ml of dry THF and added at -78° C. to a mixture of 130 mg of compound 4 and 165 μM of a 1.5 M solution of N-BuLi in hexanes in 4 ml of dry THF. After addition of about 13 mg of DMAP, the cold bath was removed and the reaction mixture stirred at 22° C. for about 2 hours. The solvent was evaporated and 4 ml of water added. After extraction with CH2Cl2 (3×10 ml), the combined organic layers were dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by column chromatography on SiO2 (EtOAc/hexanes, 1:1) to yield about 285 mg of compound 9.

Workup

  1. customThe organic solvent was evaporated
  2. extractionthe aqueous solution was extracted with Et2O (2×10 ml)
  3. extractionThe mixture was extracted again with Et2O (3×10 ml)
  4. dry with materialthe combined organic extracts were dried over Na2SO4
  5. customevaporated

Sources & evidence

ORD record
ord-ee0f71a0cf124c018293a52c1f179216
Source dataset
uspto-grants-1999_09
Patent number
US05952294

Reaction notes

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