Triethyloxonium tetrafluoroborate → [(R)-2-Benzyloxy-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

HRID 243015

Reaction equation

HRID 243015 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][C@H:8]([C:18](=O)[NH2:19])[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.C([O+](CC)CC)C.[F:34][C:35]1[CH:36]=[C:37]([NH:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=2)[C:38](N)=[CH:39][CH:40]=1>C1COCC1>[C:1]([O:5][C:6](=[O:21])[NH:7][C@H:8]([C:18]1[N:42]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=2)[C:37]2[CH:36]=[C:35]([F:34])[CH:40]=[CH:39][C:38]=2[N:19]=1)[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7216900((S)-2-Benzyloxy-1-carbamoylethyl)carbamic acid tert-butyl esterHCID 681571794-Fluoro-N2-pyridin-2-ylbenzene-1,2-diamine

Product 1

HCID 68157510[(R)-2-Benzyloxy-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl esterYield 53.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ((S)-2-benzyloxy-1-carbamoylethyl)carbamic acid tert-butyl ester (820 mg, 2.8 mmol) in anhydrous THF (10 mL) was added triethyloxonium tetrafluoroborate (550 mg, 2.9 mmol) in one portion under a nitrogen atmosphere. The resulting mixture was stirred at RT for 2 h. The volatiles were removed in vacuo and the resulting residue redissolved in absolute EtOH (10 mL). To the mixture was added 4-fluoro-N2-pyridin-2-yl-benzene-1,2-diamine (355 mg, 1.7 mmol) and the mixture stirred at 75° C. for 16 h. The volatiles were removed in vacuo and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The aqueous phase was further extracted with DCM and the combined organic fractions washed with water, dried (MgSO4) and concentrated in vacuo. The resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cHex) to afford the title compound as a yellow oil (420 mg, 53%). LCMS (Method B): RT 3.95 min [M+H]+ 463.1.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe resulting residue redissolved in absolute EtOH (10 mL)
  3. stirringthe mixture stirred at 75° C. for 16 h
  4. customThe volatiles were removed in vacuo
  5. customthe resulting residue partitioned between DCM
  6. extractionThe aqueous phase was further extracted with DCM
  7. washthe combined organic fractions washed with water
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cHex)

Sources & evidence

ORD record
ord-deb2e041a84e4f4eacd05e15f66ce7cf
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Linked notes

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