Triethylborane → N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(4S)-6-ethyl-3,4-dihydro-2H-chromen-4-yl]amino}-2-hydroxypropyl)acetamide

HRID 1985040Notes

Reaction equation

HRID 1985040 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:26]=[C:27]([F:29])[CH:28]=1)[CH2:5][C@H:6]([NH:22][C:23](=[O:25])[CH3:24])[C@H:7]([OH:21])[CH2:8][NH:9][CH:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](I)[CH:18]=2)[O:13][CH2:12][CH2:11]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].B(CC)(CC)[CH2:39][CH3:40]>C1COCC1.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:3]=[C:4]([CH:26]=[C:27]([F:29])[CH:28]=1)[CH2:5][C@H:6]([NH:22][C:23](=[O:25])[CH3:24])[C@H:7]([OH:21])[CH2:8][NH:9][C@@H:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([CH2:39][CH3:40])[CH:18]=2)[O:13][CH2:12][CH2:11]1

Participants

7

Reactant 3

HCID 7357TriethylboraneHCID 62657Potassium Phosphate, TribasicHCID 10052240N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-3,4-dihydro-2H-chromen-4-yl)amino]propyl}acetamide

Product 1

HCID 10319857N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[(4S)-6-ethyl-3,4-dihydro-2H-chromen-4-yl]amino}-2-hydroxypropyl)acetamide

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-3,4-dihydro-2H-chromen-4-yl)amino]propyl}acetamide (1.0 g, 1.9 mmol) and Pd(dppf)Cl2 (0.078 g, 0.1 mmol) was dissolved in 20 mL of degassed THF. To the mixture was added 10 mL of 2.0 M K3PO4 followed by the addition of Et3B (3.8 mL, 3.8 mmol, 1.0 M in THF) via syringe. The reaction mixture was heated to 65° C. under a nitrogen atmosphere. After 2.5 h the reaction was determined to be complete and diluted with EtOAc (100 mL) and washed with brine (3×30 mL). The organic layer was dried over Na2SO4 and conc. in vacuo to yield brown solid. The diastereomers of the title compound were separated by preparative chiral HPLC (Chiralpak AD, 20% IPA/80%heptane, 0.1% DEA). MS (ESI+) for C23H26F2N2O3 m/z 419 (M+H)+.

Workup

  1. washwashed with brine (3×30 mL)
  2. dry with materialThe organic layer was dried over Na2SO4 and conc. in vacuo
  3. customto yield brown solid
  4. customThe diastereomers of the title compound were separated by preparative chiral HPLC (Chiralpak AD, 20% IPA/80%heptane, 0.1% DEA)

Sources & evidence

ORD record
ord-7aea272dc27145018cacc9abb0678f87
Source dataset
uspto-grants-2009_06
Patent number
US07544717B2

Reaction notes

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