Water → HCID 70106026, compound

HRID 1532348Notes

Reaction equation

HRID 1532348 reaction equation
C([O:3][C:4](=[O:33])[CH2:5][N:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[C:11]([N:13]1[CH2:17][CH2:16][CH2:15][C@H:14]1[CH2:18][CH2:19][C:20]1[N:21]([CH2:31][CH3:32])[C:22]2[C:27]([CH:28]=1)=[CH:26][CH:25]=[C:24]([C:29]#[N:30])[CH:23]=2)=[O:12])C.C[Si]([N-:38][Si](C)(C)C)(C)C.[Li+].Br[CH2:45][C:46]([O:48]CC)=[O:47].O>O1CCCC1>[C:29]([C:24]1[CH:23]=[C:22]2[C:27]([CH:28]=[C:20]([CH2:19][CH2:18][C@@H:14]3[CH2:15][CH2:16][CH2:17][N:13]3[C:11]([C@H:7]3[CH2:8][CH2:9][CH2:10][N:6]3[CH:5]([C:4]([OH:3])=[O:33])[CH2:45][C:46]([OH:48])=[O:47])=[O:12])[N:21]2[CH2:31][CH3:32])=[CH:26][CH:25]=1)(=[NH:30])[NH2:38]

Participants

6

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 70106598HCID 70106598, compound

Product 1

HCID 70106026HCID 70106026, compoundYield 63.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

250 mg(0.525 mmole) of ethyl-2-[(R)-2-[[(S)-2-[2-(6-cyano-1-ethyl-indol-2-yl)ethyl]pyrrolidinyl]carbonyl]pyrrolidinyl]acetate was dissolved in 15 ml of tetrahydrofuran and then cooled to −78° C. 0.79 ml of lithium bis(trimethylsilyl)amide (1.0M solution in tetrahydrofuran) was added dropwise thereto, and the reaction mixture was stirred for 30 minutes. 0.09 ml(0.787 mmole) of ethyl bromoacetate diluted with 5 ml of tetrahydrofuran was added dropwise thereto, and the resulting mixture was stirred for one hour. After water was added, the reaction solution thereby obtained was extracted with dichloromethane. The organic layer was dried over sodium sulfate and evaporated under reduced pressure to remove the solvent. The residue was purified with silica gel column chromatography [eluent: dichloromethane/methanol(40:1)] to obtain 180 mg (Yield: 63.9%) of the title compound as a pale yellow foam.

Workup

  1. additionwas added dropwise
  2. stirringthe resulting mixture was stirred for one hour
  3. customthe reaction solution thereby obtained
  4. extractionwas extracted with dichloromethane
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. customevaporated under reduced pressure
  7. customto remove the solvent
  8. customThe residue was purified with silica gel column chromatography [eluent: dichloromethane/methanol(40:1)]

Sources & evidence

ORD record
ord-5a3c5ca72bf84e42ae33bc004120dc68
Source dataset
uspto-grants-2001_03
Patent number
US06201006B1

Reaction notes

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