Ethyl Acetate → 4-[4-(2-fluoro-benzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1270102Notes

Reaction equation

HRID 1270102 reaction equation
Br[C:2]1[C:11]2[O:10][C:9]([CH3:13])([CH3:12])[CH2:8][N:7]([S:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])(=[O:16])=[O:15])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:24]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].CC([O-])(C)C.[Na+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([O:26][C:24]([N:31]1[CH2:36][CH2:35][N:34]([C:2]2[C:11]3[O:10][C:9]([CH3:13])([CH3:12])[CH2:8][N:7]([S:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[F:23])(=[O:16])=[O:15])[C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH2:33][CH2:32]1)=[O:25])([CH3:30])([CH3:28])[CH3:29]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 225572828-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazineHCID 23676156Sodium t-butoxide

Product 1

HCID 588421354-[4-(2-fluoro-benzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl]-piperazine-1-carboxylic acid tert-butyl esterYield 82.7%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

A solution of 8-bromo-4-(2-fluoro-benzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine (450 mg, 1.124 mmol) and 1-Boc-piperazine (209.4 mg, 1.124 mmol) in 5 mL of toluene was added to a warm, degassed mixture of Pd2(dba)3(Tris(dibenzylideneacetone)dipalladium(0), 20.59 mg, 0.022 mmol), BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, 35.0 mg, 0.056 mmol) and NaOt-Bu (151.26 mg, 1.57 mmol) in 5 ml of toluene. With stirring, the solution was heated at 90° C. for 2 hours, and then allowed to cool to room temperature. Ethyl acetate was added to the reaction which was then filtered through celite. The filtrate was washed with water (2×15 ml), brine (1×15 ml), and dried over MgSO4, after which the organic fraction was concentrated in vacuo. The resulting residue was purified by flash chromatography (15%–30% Ethyl acetate/Hexane) to give 470 mg (0.93 mmol) of 4-[4-(2-fluoro-benzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl]-piperazine-1-carboxylic acid tert-butyl ester. MS: (M+H) 506.

Workup

  1. customdegassed
  2. temperatureto cool to room temperature
  3. filtrationwas then filtered through celite
  4. washThe filtrate was washed with water (2×15 ml), brine (1×15 ml)
  5. dry with materialdried over MgSO4
  6. concentrationafter which the organic fraction was concentrated in vacuo
  7. customThe resulting residue was purified by flash chromatography (15%–30% Ethyl acetate/Hexane)

Sources & evidence

ORD record
ord-ba0eb1bdddf044958b4c73be1e8da8ac
Source dataset
uspto-grants-2007_04
Patent number
US07202241B2

Reaction notes

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