N-bromobutanimide → rac-(7aR,11aS)-2-bromo-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2'-[1,3]dioxolan]-3-amine

HRID 718828Notes

Reaction equation

HRID 718828 reaction equation
[CH2:1]([C:3]12[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH:9]1[CH2:8][CH2:7][O:6][C:5]1[CH:18]=[C:19]([NH2:22])[CH:20]=[CH:21][C:4]2=1)[CH3:2].C1C(=O)N([Br:30])C(=O)C1>C1COCC1>[Br:30][C:20]1[C:19]([NH2:22])=[CH:18][C:5]2[O:6][CH2:7][CH2:8][CH:9]3[CH2:10][C:11]4([O:15][CH2:14][CH2:13][O:12]4)[CH2:16][CH2:17][C:3]3([CH2:1][CH3:2])[C:4]=2[CH:21]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 86722434rac-(7aR,11aS)-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2'-[1,3]dioxolan]-3-amine

Product 1

HCID 86722436rac-(7aR,11aS)-2-bromo-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2'-[1,3]dioxolan]-3-amineYield 96.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of rac-(7aR,11aS)-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2′-[1,3]dioxolan]-3-amine (86, R2=Ethyl) (11.2 g, 37.0 mmol) in THF (370 mL) was cooled to about −10° C. in a salt/ice bath and was then treated with NBS (6.59 g, 37.0 mmol) with stirring for about 5 min. The reaction was quenched by addition of sat. aq. NaHCO3 (250 mL), and the mixture was diluted with EtOAc (350 mL). The aqueous phase was extracted with EtOAc (2×50 mL) and the combined organic phases were washed with brine (350 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified on silica gel (220 g, eluted with 0% to 40% EtOAc in heptane). Collection and concentration of the appropriate fractions gave rac-(7aR,11aS)-2-bromo-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2′-[1,3]dioxolan]-3-amine (87, R2=Ethyl) (13.6 g, 96%) containing about 20% of a minor regioisomer. The material was used directly in Step #4 without further purification. LC/MS, method 3, 2.49 min, MS m/z 382, 384 (M+H)+.

Workup

  1. customThe reaction was quenched by addition of sat. aq. NaHCO3 (250 mL)
  2. additionthe mixture was diluted with EtOAc (350 mL)
  3. extractionThe aqueous phase was extracted with EtOAc (2×50 mL)
  4. washthe combined organic phases were washed with brine (350 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified on silica gel (220 g, eluted with 0% to 40% EtOAc in heptane)
  9. customCollection and concentration of the appropriate fractions

Sources & evidence

ORD record
ord-e1bdfe91887e4261b8b0e58393936285
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

Loading…