1-Bromo-2-Chloroethane → HCID 89886644, compound

HRID 338639Notes

Reaction equation

HRID 338639 reaction equation
[C@H:1]12[CH2:7][C@H:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH2:24][CH2:25][Cl:26]>>[Cl:26][CH2:25][CH2:24][N:5]1[CH2:6][C@@H:1]2[CH2:7][C@H:4]1[CH2:3][N:2]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9]

Participants

4

Reactant 3

HCID 78491-Bromo-2-Chloroethane2×HCID 62657Potassium Phosphate, TribasicHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptane

Product 1

HCID 89886644HCID 89886644, compoundYield 67.3%

Conditions

Temperature
55 °C

Procedure

(1S,4S)-tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (525 mg, 2.65 mmol) and potassium phosphate (1686 mg, 7.94 mmol) were combined in a 75 mL medium pressure flask and purged in a 50° C. vacuum oven for 10 mins and placed under N2 (g) atmosphere. THF (30 mL) was added, followed by 1-bromo-2-chloroethane (1.124 mL, 13.24 mmol) and the mixture was heated to 55° C. for 18 h. The reaction mixture was cooled to rt, treated with more 1-bromo-2-chloroethane (0.043 mL, 0.517 mmol) and heated back up to 55° C. for 68 h. The reaction was filtered and washed with DCM. The liquid filtrate was concentrated to viscous brown oil which was purified by column chromatography (SiO2, 40 g cartridge, eluted with 95:5 DCM:MeOH), dried under vacuum with stirring to give (1S,4S)-tert-butyl 5-(2-chloroethyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (465 mg, 1.783 mmol, 67.3% yield) as viscous light brown oil. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.37 (s, 1H), 4.36 (br. s., 1H), 4.24 (br. s., 1H), 3.44 (d, J=9.5 Hz, 1H), 3.17 (t, J=8.8 Hz, 1H), 3.08-2.94 (m, 1H), 2.93-2.85 (m, 2H), 2.67 (d, J=9.5 Hz, 1H), 2.53 (d, J=9.5 Hz, 1H), 1.82 (d, J=6.4 Hz, 1H), 1.71 (dd, J=15.9, 9.8 Hz, 1H), 1.46 (s, 9H).

Workup

  1. custompurged in a 50° C. vacuum oven for 10 mins
  2. additionTHF (30 mL) was added
  3. temperatureThe reaction mixture was cooled to rt
  4. temperatureheated back up to 55° C. for 68 h
  5. filtrationThe reaction was filtered
  6. washwashed with DCM
  7. concentrationThe liquid filtrate was concentrated to viscous brown oil which
  8. customwas purified by column chromatography (SiO2, 40 g cartridge, eluted with 95:5 DCM:MeOH)
  9. customdried under vacuum

Sources & evidence

ORD record
ord-e6ae7e0ee20741b1b0caad7193165e3d
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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