N,O-bis(trimethylsilyl)acetamide → HCID 178445557, compound

HRID 1857544Notes

Reaction equation

HRID 1857544 reaction equation
[CH2:1]([O:8][C:9]([CH:11]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:12][PH:13](=[O:15])[OH:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:20]([C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH3:35]/C(/O[Si](C)(C)C)=N\[Si](C)(C)C>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:10])[CH:11]([CH2:12][PH:13]([O:14][CH2:35][CH2:31][C:30]1[CH:33]=[CH:34][C:27]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:28][CH:29]=1)=[O:15])[CH2:16][CH:17]([CH3:19])[CH3:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 100382674-Benzylbenzyl bromideHCID 178445562HCID 178445562, compound

Product 1

HCID 178445557HCID 178445557, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(2-Benzyloxycarbonyl-4-methylpentyl)phosphinic acid (1.14 grams, 4.0 mmole), 4-benzylbenzyl bromide (1.31 grams, 5.0 mmole) and N,O-bis(trimethylsilyl) acetamide (2.44 grams, 12 mmole) were combined in dry methylene chloride (40 ml); the mixture was degassed with a stream of dry nitrogen, then stirred at room temperature for 18 hours and refluxed for 24 hours. The cooled solution was quenched with 1N hydrochloric acid (25 ml). The methylene chloride layer was separated and washed with 1N hydrochloric acid (2×25 ml), dried with magnesium sulfate, filtered and concentrated to a turbid oil. This was dissolved in methanol (10 ml)/toluene (40 ml) and treated with excess trimethylsilyldiazomethane (commercial hexane solution). After 30 minutes the excess trimethylsilyldiazo-methane was destroyed with acetic acid. The solution was concentrated to an oil which was chromatographed (75:25--ethyl acetate:hexane) to give 1.18 grams (62%) of 2-[(4-benzylbenzyl)methoxyphosphinoylmethyl]-4-methylpentanoic acid benzyl ester as a colorless oil.

Workup

  1. customthe mixture was degassed with a stream of dry nitrogen
  2. temperaturerefluxed for 24 hours
  3. customThe cooled solution was quenched with 1N hydrochloric acid (25 ml)
  4. customThe methylene chloride layer was separated
  5. washwashed with 1N hydrochloric acid (2×25 ml)
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to a turbid oil
  9. dissolutionThis was dissolved in methanol (10 ml)/toluene (40 ml)
  10. additiontreated with excess trimethylsilyldiazomethane (commercial hexane solution)
  11. customAfter 30 minutes the excess trimethylsilyldiazo-methane was destroyed with acetic acid
  12. concentrationThe solution was concentrated to an oil which
  13. customwas chromatographed (75:25--ethyl acetate:hexane)

Sources & evidence

ORD record
ord-2c70a0d41a36445580f4979d8a66c665
Source dataset
uspto-grants-2000_11
Patent number
US06147061

Reaction notes

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