Hydrochloric Acid → ethyl (5S)-3-(4-bromobenzyl)-5-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-phenylethyl}-2-oxotetrahydro-3-furancarboxylate

HRID 1174261Notes

Reaction equation

HRID 1174261 reaction equation
O1C[C@H]1[C@@H:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:20]([O:28][CH2:29][CH3:30])(=[O:27])[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23].CC[O-].[Na+].[Br:35][C:36]1[CH:43]=[CH:42][C:39]([CH2:40]Br)=[CH:38][CH:37]=1.Cl>C(O)C>[Br:35][C:36]1[CH:43]=[CH:42][C:39]([CH2:40][C:21]2([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:30][C@@H:29]([C@@H:4]([NH:12][C:13]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:19])[CH2:5][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=3)[O:28][C:20]2=[O:27])=[CH:38][CH:37]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 685274-Bromobenzyl bromideHCID 2723922Sodium ethoxideHCID 9813904tert-Butyl {(1S)-1-[(2R)-oxiran-2-yl]-2-phenylethyl}carbamate

Product 1

HCID 67406735ethyl (5S)-3-(4-bromobenzyl)-5-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-phenylethyl}-2-oxotetrahydro-3-furancarboxylateYield 107.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of tert-Butyl(1S)-1-[(2R)-oxiran-2-yl]-2-phenylethylcarbamate (10.0 g, 38.0 mmol) and diethyl malonate (5.8 ml, 38.2 mmol) in ethanol (30 mL) at 0° C. was treated with a solution of NaOEt (13.5 mL, 21% in ethanol) over 10 minutes. The reaction was warmed to 25° C. and stirred for 18 hours. The reaction was re-cooled to 0° C. and treated with a solution of 4-bromobenzyl bromide (9.5 g, 38.0 mmol) in ethanol (40 mL), stirred at 50° C. for 3 hours, cooled to 0° C. and adjusted to neutral pH by addition of 4N HCl. The ethanol was removed under reduced pressure and the residue was partitioned between chloroform and water. The organic phase was washed with brine and dried over MgSO4, filtered and concentrated to give the title compound (22.4 g), which was used without further purification.

Workup

  1. temperatureThe reaction was re-cooled to 0° C.
  2. stirringstirred at 50° C. for 3 hours
  3. temperaturecooled to 0° C.
  4. customThe ethanol was removed under reduced pressure
  5. customthe residue was partitioned between chloroform and water
  6. washThe organic phase was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-e82009b8282f458aa40f266ca1db314b
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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