Bis(2-bromoethyl) ether → HCID 86687329, compound

HRID 537004Notes

Reaction equation

HRID 537004 reaction equation
Br[CH2:2][CH2:3][O:4][CH2:5][CH2:6]Br.[CH2:8]([NH:15][S:16]([CH2:19][C@:20]12[C:26]([CH3:28])([CH3:27])[C@H:23]([CH2:24][CH2:25]1)[CH2:22][C@H:21]2[NH2:29])(=[O:18])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(N(CC)C(C)C)(C)C>CN(C)C(=O)C.C1(C)C=CC=CC=1>[CH2:8]([NH:15][S:16]([CH2:19][C@:20]12[C:26]([CH3:27])([CH3:28])[C@H:23]([CH2:24][CH2:25]1)[CH2:22][C@H:21]2[N:29]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)(=[O:18])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 21521Bis(2-bromoethyl) etherHCID 81531DiisopropylethylamineHCID 86687330HCID 86687330, compound

Product 1

HCID 86687329HCID 86687329, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 31374DimethylacetamideSolvent

Procedure

Bis(2-bromoethyl)ether (18.3 mL, 146 mmol) was added to a solution of (1S,2R,4R)—N-benzyl-2-amino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide (VIa) (23.5 g, 72.9 mmol) and N,N-Diisopropylethylamine (DIPEA) (55.8 mL, 320 mmol) in N,N-dimethylacetamide (DMAC) (470 mL). The solution was heated at 120° C. until the amine (1S,2R,4R)—N-benzyl-2-amino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide (VIa) was <2% by HPLC analysis. The mixture was cooled to ambient temperature and diluted with toluene (470 mL) and was extracted with water (470 mL). After layer separation, the toluene layer was washed twice with 10% aq. NaCl (230 mL each) and concentrated to give the crude product as a brown solid. The sulfonamide (1S,2R,4R)—N-benzyl-2-morpholino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide (IIa) was crystallized from a mixture of toluene (23 mL) and n-heptane (47 mL) by slowly cooling from 75° C. to 60° C., stirring at 60° C. for an hour and then cooling to ambient temperature, followed by the addition of n-heptane (70 mL) and stirring for an hour. The suspension was filtered and the powder was washed with a mixture of toluene and n-heptane (1:5, 47 mL) to give (1S,2R,4R)—N-benzyl-2-morpholino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide (IIa) as an orange to light brown powder (22.2 g; 78%; 98.9% pure as assessed by HPLC).

Workup

  1. extractionwas extracted with water (470 mL)
  2. customAfter layer separation
  3. washthe toluene layer was washed twice with 10% aq. NaCl (230 mL each)
  4. concentrationconcentrated
  5. customto give the crude product as a brown solid
  6. customThe sulfonamide (1S,2R,4R)—N-benzyl-2-morpholino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide (IIa) was crystallized from a mixture of toluene (23 mL) and n-heptane (47 mL)
  7. temperatureby slowly cooling from 75° C. to 60° C.
  8. temperaturecooling to ambient temperature
  9. additionfollowed by the addition of n-heptane (70 mL)
  10. stirringstirring for an hour
  11. filtrationThe suspension was filtered
  12. washthe powder was washed with a mixture of toluene and n-heptane (1:5, 47 mL)

Sources & evidence

ORD record
ord-956e6ecaf3f24425a9aaf00490d75774
Source dataset
uspto-grants-2014_10
Patent number
US08859765B2

Reaction notes

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