Boron tribromide → N-(t-butoxycarbonyl)-(+/-)-1,3,4,10b-tetrahydro-9-hydroxy-7-trifluoromethoxy-pyrazino[2,1-a]isoindol-6(2H)-one

HRID 1159062Notes

Reaction equation

HRID 1159062 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:28][CH2:27][N:11]2[C:12](=[O:26])[C:13]3[C:18]([CH:10]2[CH2:9]1)=[CH:17][C:16]([O:19]C)=[CH:15][C:14]=3[O:21][C:22]([F:25])([F:24])[F:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].B(Br)(Br)Br.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:28][CH2:27][N:11]2[C:12](=[O:26])[C:13]3[C:18]([CH:10]2[CH2:9]1)=[CH:17][C:16]([OH:19])=[CH:15][C:14]=3[O:21][C:22]([F:24])([F:25])[F:23])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 90495Di-tert-butyl dicarbonateHCID 68687866N-(t-butoxycarbonyl)-(+/-)-1,3,4,10b-tetrahydro-9-methoxy-7-trifluoromethoxy-pyrazino[2,1-a]isoindol-6(2H)-one

Product 1

HCID 68690753N-(t-butoxycarbonyl)-(+/-)-1,3,4,10b-tetrahydro-9-hydroxy-7-trifluoromethoxy-pyrazino[2,1-a]isoindol-6(2H)-oneYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirring solution of N-(t-butoxycarbonyl)-(±)-1,3,4,10b-tetrahydro-9-methoxy-7-trifluoromethoxy-pyrazino[2,1-a]isoindol-6(2H)-one (201 mg, 0.5 mmol) in dry CH2Cl2 (3 mL) at −78° C. under Ar was added IM boron tribromide in CH2Cl2 (1.75 mL). The reaction was stirred for 1 h and then warmed to room temperature for 18 h. The reaction was refluxed for 24 h and then quenched with water. The reaction was stirred for 30 min and then conc. in vacuo to a brown solid. The solid was treated with 6M HCl. After 1 h, the reaction was conc. in vacuo to a brown solid. The solid was partioned between water and EtOAc, basified with sodium bicarbonate, and treated with di-t-butyl dicarbonate (109 mg, 0.5 mmol). The reaction was stirred for 1 h and extracted with EtOAc (3×10 mL). The organic layers were combined, dried over MgSO4, and conc. in vacuo to a brown solid. The solid was purified by trituration with chloroform to yield 103 mg of the desired product as a white solid. MS (ESI) 389 (M+H).

Workup

  1. temperatureThe reaction was refluxed for 24 h
  2. customquenched with water
  3. stirringThe reaction was stirred for 30 min
  4. additionThe solid was treated with 6M HCl
  5. waitAfter 1 h
  6. stirringThe reaction was stirred for 1 h
  7. extractionextracted with EtOAc (3×10 mL)
  8. dry with materialdried over MgSO4
  9. customThe solid was purified by trituration with chloroform

Sources & evidence

ORD record
ord-e15ddd24676f4eb2a68ccf0298f64247
Source dataset
uspto-grants-2010_10
Patent number
US07812024B2

Reaction notes

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