Acetonitrile → HCID 131737189, compound

HRID 62232Notes

Reaction equation

HRID 62232 reaction equation
[P:1]([O:19][CH2:20]Cl)([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH2:22]([N:29]([C@@:41]([CH3:68])([CH2:52][C:53]1[CH:58]=[CH:57][C:56]([OH:59])=[C:55]([O:60][CH2:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH:54]=1)[C:42]([O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:43])[NH:30][C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(#N)C.N12CCCN=C1CCCCC2>O>[CH2:22]([N:29]([C@@:41]([CH3:68])([CH2:52][C:53]1[CH:58]=[CH:57][C:56]([O:59][CH2:20][O:19][P:1]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)([O:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:2])=[C:55]([O:60][CH2:61][C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)[CH:54]=1)[C:42]([O:44][CH2:45][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)=[O:43])[NH:30][C:31]([O:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:32])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 11484214Dibenzyl chloromethyl phosphateHCID 124130654(S)-benzyl 2-benzyl-2-(1-(benzyloxy)-3-(3-(benzyloxy)-4-hydroxyphenyl)-2-methyl-1-oxopropan-2-yl)hydrazinecarboxylate2×

Product 1

HCID 131737189HCID 131737189, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 100 mL round bottom flask were added dibenzyl (chloromethyl) phosphate (1.632 g, 4.99 mmol), (S)-benzyl 2-benzyl-2-(1-(benzyloxy)-3-(3-(benzyloxy)-4-hydroxyphenyl)-2-methyl-1-oxopropan-2-yl)hydrazinecarboxylate, Compound 2, (2.1 g, 3.33 mmol) and 25 mL acetonitrile. The mixture was cooled in an ice bath. 1,8-Diazabicyclo[5.4.0]undec-7-ene (0.745 mL, 4.99 mmol) was added, and the mixture was stirred in the ice bath for 30 minutes, then at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate twice. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated. The crude was purified first by flash chromatography using a 120 g silica column (0-50% ethyl acetate in heptanes), followed by RP-HPLC (60-100% acetonitrile in 0.1% TFA/water on Phenonemex C18 5 u column) to afford Compound 3 as a colorless oil (247 mg, 8%).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. customat room temperature
  3. customovernight
  4. extractionthe mixture was extracted with ethyl acetate twice
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe crude was purified first by flash chromatography

Sources & evidence

ORD record
ord-967c8d0010d84551a695b32202a2ba3e
Source dataset
uspto-grants-2016_09
Patent number
US09446059B2

Reaction notes

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