Bromobenzene → tert-Butyl 6-benzyl-6-hydroxy-1,4-oxazepane-4-carboxylate

HRID 401815Notes

Reaction equation

HRID 401815 reaction equation
C([Li])CCC.CCCCCC.Br[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C1(CO[CH2:24][C:25]2([OH:39])[CH2:31][O:30][CH2:29][CH2:28][N:27]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:26]2)CC1.S([O-])(O)(=O)=O.[Na+]>C1COCC1>[CH2:24]([C:25]1([OH:39])[CH2:31][O:30][CH2:29][CH2:28][N:27]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:26]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 5

HCID 7961BromobenzeneHCID 8058HexaneHCID 516919Sodium BisulfateHCID 68531565Tert-butyl 6-[(cyclopropylmethoxy)methyl]-6-hydroxy-1,4-oxazepane-4-carboxylateHCID 178418339Butyllithium

Product 1

HCID 57732098tert-Butyl 6-benzyl-6-hydroxy-1,4-oxazepane-4-carboxylateYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-80 °C

Procedure

1.6M solution of butyl lithium in hexane (150 mL, 0.24 mol, 1.1 eq) was added to a solution of bromobenzene (25.3 mL, 0.24 mol, 1.1 eq) in THF (200 mL) at −60° C. in a stream of argon. The reaction mixture was cooled to −80° C., and a solution of tert-butyl 6-[(cyclopropylmethoxy)methyl]-6-hydroxy-1,4-oxazepane-4-carboxylate (Preparation 80, 50 g, 0.22 mol, 1 eq) in THF was added. Then the mixture was cooled to −100° C., and a solution of etherate (30.4 g, 0.24 mol, 1.1 eq) was added at this temperature for 30 min. The reaction mixture was heated to 0° C. for 5 h, and 5M sodium hydrogen sulfate solution (50 mL) was added. The organic layer was separated, evaporated, and the residue was distributed between water and ether. The organic layer was separated, washed with water and brine, dried, evaporated, and the residue was dissolved in MeOH (200 mL). Ethylenediamine (30 mL) was added to the mixture, which was heated until boiled, cooled, evaporated, and coevaporated with dioxane. The residue was purified by chromatography on silica (1 L; carbon tetrachloride→chloroform, then MeOH 5%), evaporated and dried to give title compound (37.15 g, 0.12 mol, 55%).

Workup

  1. temperatureThen the mixture was cooled to −100° C.
  2. additiona solution of etherate (30.4 g, 0.24 mol, 1.1 eq) was added at this temperature for 30 min
  3. temperatureThe reaction mixture was heated to 0° C. for 5 h
  4. customThe organic layer was separated
  5. customevaporated
  6. customThe organic layer was separated
  7. washwashed with water and brine
  8. customdried
  9. customevaporated
  10. dissolutionthe residue was dissolved in MeOH (200 mL)
  11. additionEthylenediamine (30 mL) was added to the mixture, which
  12. temperaturewas heated
  13. temperaturecooled
  14. customevaporated
  15. customThe residue was purified by chromatography on silica (1 L
  16. customcarbon tetrachloride→chloroform, then MeOH 5%), evaporated
  17. customdried

Sources & evidence

ORD record
ord-03bf03c0cf27475ca4b0936c9ea71318
Source dataset
uspto-grants-2014_06
Patent number
US08741934B2

Reaction notes

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