Acetic Anhydride → 6-[Acetoxy-(10-benzyl-11-oxo-10,11-dihydro-dibenzo[b,f][1,4]oxazepin-8-yl)-methyl]-6-bromo-7oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

HRID 638857Notes

Reaction equation

HRID 638857 reaction equation
[CH2:1]([N:8]1[C:14](=[O:15])[C:13]2[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=2[O:11][C:10]2[CH:20]=[CH:21][C:22]([CH:24]=[O:25])=[CH:23][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br-].[Mg+2].[Br-].[N+:29]([C:32]1[CH:50]=[CH:49][C:35]([CH2:36][O:37][C:38]([C:40]2[N:41]3[C@H:44]([S:45][CH:46]=2)[C@@H:43]([Br:47])[C:42]3=[O:48])=[O:39])=[CH:34][CH:33]=1)([O-:31])=[O:30].C(N(CC)CC)C.[C:58](OC(=O)C)(=[O:60])[CH3:59]>C(#N)C.CN(C1C=CN=CC=1)C.C1COCC1>[N+:29]([C:32]1[CH:50]=[CH:49][C:35]([CH2:36][O:37][C:38]([C:40]2[N:41]3[CH:44]([S:45][CH:46]=2)[C:43]([CH:24]([O:25][C:58](=[O:60])[CH3:59])[C:22]2[CH:21]=[CH:20][C:10]4[O:11][C:12]5[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=5[C:14](=[O:15])[N:8]([CH2:1][C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=5)[C:9]=4[CH:23]=2)([Br:47])[C:42]3=[O:48])=[O:39])=[CH:34][CH:33]=1)([O-:31])=[O:30]

Participants

9

Reactant 5

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 82241Magnesium BromideHCID 11280588(5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl esterHCID 2222449110-Benzyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]oxazepine-8-carbaldehyde

Product 1

HCID 684449316-[Acetoxy-(10-benzyl-11-oxo-10,11-dihydro-dibenzo[b,f][1,4]oxazepin-8-yl)-methyl]-6-bromo-7oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl esterYield 41%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

10-benzyl-11-oxo-10,11-dihydro-dibenzo[b,f][1,4]oxazepine-8-carbaldehyde (0.250 g, 0.759 mmole) in acetonitrile was added to magnesium bromide (0.419 g, 2.28 mmole) under N2 at room temperature. The dry THF solution of (5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl ester (0.292 g, 0.758 mmole) then was added to the mixture. After 15 minutes the reaction mixture was cooled to −20° C., and triethylamine (0.317 mL, 2.27 mmole) was added. The reaction flask was covered with foil to exclude light. After 4 hours at −20° C., treated with acetic anhydride (0.358 mL, 3.795 mmole) and DMAP (0.00927 g, 0.0759 mmole). Warmed up the reaction mixture to 0° C. and placed it in freezer overnight. Reaction solution was concentrated and dissolved with ethyl acetate and washed with 5% of citric acid aqueous solution, saturated NaHCO3, water and brine. Organic layer was dried in sodium sulfate and filtered and concentrated. Purified with silica gel column and 1:15 ethyl acetate/CH2Cl2. Obtained the desired compound (light yellow oil) in 41% yield.

Workup

  1. temperatureWarmed up the reaction mixture to 0° C.
  2. customin freezer overnight
  3. customReaction solution
  4. concentrationwas concentrated
  5. dissolutiondissolved with ethyl acetate
  6. washwashed with 5% of citric acid aqueous solution, saturated NaHCO3, water and brine
  7. dry with materialOrganic layer was dried in sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurified with silica gel column and 1:15 ethyl acetate/CH2Cl2

Sources & evidence

ORD record
ord-d30de33b6ba34b2d9094be075b84bee8
Source dataset
uspto-grants-2010_04
Patent number
US07691842B2

Reaction notes

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