Hexamethylphosphoramide → HCID 18610531, compound

HRID 256005Notes

Reaction equation

HRID 256005 reaction equation
[H-].[Na+].CN(C)P(=O)(N(C)C)N(C)C.[O:14]=[C:15]1[C@@H:21]([N:22]2[C:26](=[O:27])[C:25]3=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]3[C:23]2=[O:32])[CH2:20][S:19][CH2:18][C@@H:17]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[NH:16]1.Br[CH2:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]>CN(C)C=O.C(OCC)(=O)C>[O:14]=[C:15]1[C@@H:21]([N:22]2[C:23](=[O:32])[C:24]3=[CH:31][CH:30]=[CH:29][CH:28]=[C:25]3[C:26]2=[O:27])[CH2:20][S:19][CH2:18][C@@H:17]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:16]1[CH2:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]

Participants

7

Reactant 4

HCID 12679HexamethylphosphoramideHCID 24758Sodium hydride2×HCID 79177tert-Butyl bromoacetate2×HCID 13605646HCID 13605646, compound

Product 1

HCID 18610531HCID 18610531, compoundYield 65.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

270 mg of a 50% w/w suspension of sodium hydride in mineral oil were added to a solution containing 5 ml of hexamethylphosphoric triamide and 1.9 g of 5-oxo-3(R)-phenyl-6(R)-phthalimidoperhydro-1,4-thiazepine [prepared as described in step (e) above] dissolved in 20 ml of dimethylformamide, and the mixture was stirred for 5 minutes at room temperature, 1.8 g of t-butyl bromoacetate was then added to the mixture. The resulting mixture was stirred for 1 hour at room temperature, after which a further 0.2 g of a 55% w/w suspension of sodium hydride in oil and 1 g of t-butyl bromoacetate were added. The mixture was stirred for a further 1 hour at room temperature. Ethyl acetate was then added to the mixture, and the mixture was washed with an aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate, after which the solvent was distilled off. The residue was subjected to silica gel column chromatography, using a 1:40 by volume mixture of ethyl acetate and methylene chloride as eluent, to give 1.65 g of the title compound as an amorphous substance.

Workup

  1. additionwere added to a solution
  2. stirringThe resulting mixture was stirred for 1 hour at room temperature
  3. additionwere added
  4. stirringThe mixture was stirred for a further 1 hour at room temperature
  5. washthe mixture was washed with an aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationafter which the solvent was distilled off
  8. additionby volume mixture of ethyl acetate and methylene chloride as eluent

Sources & evidence

ORD record
ord-dfc2c9df1fc14daf96be035c14180274
Source dataset
uspto-grants-1987_10
Patent number
US04699905

Reaction notes

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