Trimethyl borate → Ammonia

HRID 2387686Notes

Reaction equation

HRID 2387686 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]([CH:38]=[CH:39][CH:40]=1)[CH2:10][O:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]([CH3:37])([CH3:36])[CH2:19][CH2:20][C:21]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:22]#[N:23])[CH2:14][CH2:13]1.C[O:42]B(OC)OC.C[N+]1([O-])CCOCC1>O1CCCC1>[NH3:15].[OH:42][C:7]1[CH:8]=[C:9]([CH:38]=[CH:39][CH:40]=1)[CH2:10][O:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]([CH3:37])([CH3:36])[CH2:19][CH2:20][C:21]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:22]#[N:23])[CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 8470Trimethyl borateHCID 82029Methyl morpholine oxideHCID 59423969HCID 59423969, compoundHCID 178418339Butyllithium

Product 2

HCID 222AmmoniaHCID 59423983HCID 59423983, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (2.5M in hexanes, 0.18 mL, 0.45 mmol) was added dropwise to a solution of the product of example 87 (200 mg, 0.38 mmol) in tetrahydrofuran (5 mL), cooled to −78° C., and the mixture was stirred for 15 minutes. Trimethylborate (0.13 mL, 1.13 mmol) was added and the mixture was stirred at −78° C. for 30 minutes and at room temperature for 2 hours. 4-methylmorpholine N-oxide (132 mg, 1.13 mmol) was added and the mixture was heated under reflux for 4 hours and stirred at room temperature for 18 hours. The reaction mixture was then partitioned between ethyl acetate (30 mL) and water (30 mL) and the organic layer was separated and washed with water (20 mL). The organic solution was dried over sodium sulfate, concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with dichloromethane:methanol:0.88 ammonia, 100:0:0 to 90:10:1. The appropriate fractions were evaporated under reduced pressure and the residue was further purified by preparative tlc, eluting with dichloromethane:methanol:0.88 ammonia, 90:10:1, to afford the title compound as a gum in 3% yield, 5 mg.

Workup

  1. stirringthe mixture was stirred at −78° C. for 30 minutes and at room temperature for 2 hours
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 4 hours
  4. stirringstirred at room temperature for 18 hours
  5. customThe reaction mixture was then partitioned between ethyl acetate (30 mL) and water (30 mL)
  6. customthe organic layer was separated
  7. washwashed with water (20 mL)
  8. dry with materialThe organic solution was dried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customthe residue was purified by column chromatography on silica gel
  11. washeluting with dichloromethane
  12. customThe appropriate fractions were evaporated under reduced pressure
  13. customthe residue was further purified by preparative tlc
  14. washeluting with dichloromethane

Sources & evidence

ORD record
ord-00855b7c000d43259b2bab9f6481f38a
Source dataset
uspto-grants-2012_09
Patent number
US08268881B2

Reaction notes

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