Dichloromethane → HCID 86632036, compound

HRID 1092924Notes

Reaction equation

HRID 1092924 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1.ClCCl.[CH2:22]([O:29][C:30]([NH:32][CH:33]([CH2:44][CH2:45][P:46](OCl)([O:48][CH3:49])=[O:47])[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35])=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>CCOC(C)=O.CCCCCC>[CH2:22]([O:29][C:30]([NH:32][CH:33]([CH2:44][CH2:45][P:46]([O:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][C:9]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:10])[CH:3]=1)([O:48][CH3:49])=[O:47])[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35])=[O:31])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 7016416BENZYL 3-HYDROXYPHENYLACETATEHCID 86632037HCID 86632037, compound

Product 1

HCID 86632036HCID 86632036, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
0 °C

Procedure

Benzyl 3-hydroxyphenylacetate 0.88 g (3.60 mmol) was added to 30 mL of a dry dichloromethane solution containing 3.60 mmol of benzyl 2-(N-benzyloxycarbonylamino)-4-[chloro(methyl)phosphono]butanoate obtained in the same manner as Example 1. After the solution was cooled to 0° C., 0.51 mL (3.60 mmol) of triethylamine was added and stirred at 0° C. for 15 minutes. Thereafter, the temperature was increased and reaction was carried out at 34° C. for 45 minutes. After the completion of the reaction was confirmed by TLC (EtOAc/hexane=1:1), the reaction mixture was vacuum-concentrated and the residue was dissolved in 30 mL of ethyl acetate and the insoluble salt was removed by filtration. The filtrate was vacuum-concentrated, and the crude product was purified by flash column chromatography on neutral silica gel 60 N using a solvent mixture of ethyl acetate and hexane at 4:3 to obtain benzyl 2-(N-benzyloxycarbonylamino)-4-{[3-(benzyloxycarbonylmethyl)phenyl] (methyl)phosphono}butanoate as a colorless oily substance (0.72 g, yield 31%).

Workup

  1. customobtained in the same manner as Example 1
  2. temperatureThereafter, the temperature was increased
  3. customreaction
  4. waitwas carried out at 34° C. for 45 minutes
  5. concentrationthe reaction mixture was vacuum-concentrated
  6. dissolutionthe residue was dissolved in 30 mL of ethyl acetate
  7. customthe insoluble salt was removed by filtration
  8. concentrationThe filtrate was vacuum-concentrated
  9. customthe crude product was purified by flash column chromatography on neutral silica gel 60 N
  10. additiona solvent mixture of ethyl acetate and hexane at 4:3

Sources & evidence

ORD record
ord-f155f80994c64f11afb9f2bb6a405bfd
Source dataset
uspto-grants-2012_03
Patent number
US08129557B2

Reaction notes

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