Iodine → tert-Butyl(3R)-3-(tert-butoxycarbonylamino)-4-(5-hydroxy-2-methyl-phenyl)-butanoate

HRID 1053664Notes

Reaction equation

HRID 1053664 reaction equation
II.C[Si](Cl)(C)C.[C:8]([O:12][C:13]([NH:15][C@H:16]([CH2:25]I)[CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:14])([CH3:11])([CH3:10])[CH3:9].I[C:28]1[CH:29]=[C:30]([OH:35])[CH:31]=[CH:32][C:33]=1[CH3:34].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C)C=O.[Zn]>[C:8]([O:12][C:13]([NH:15][C@H:16]([CH2:25][C:32]1[CH:31]=[C:30]([OH:35])[CH:29]=[CH:28][C:33]=1[CH3:34])[CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:14])([CH3:11])([CH3:10])[CH3:9]

Participants

8

Reactant 5

HCID 807Iodine2×HCID 6397Chlorotrimethylsilane2×HCID 80271Tri-o-tolylphosphineHCID 534256963-Iodo-4-methylphenolHCID 86222841tert-Butyl (S)-3-(Boc-amino)-4-iodobutanoate2×

Product 1

HCID 118276719tert-Butyl(3R)-3-(tert-butoxycarbonylamino)-4-(5-hydroxy-2-methyl-phenyl)-butanoate

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst3×HCID 6228DimethylformamideSolvent

Procedure

Following the General Procedure of Description 15 (Part A), zinc dust (Zn) (392 mg, 6.0 mmol) is activated with elemental iodine (I2) (38 mg, 0.15 mmol, 15 mol-%) and trimethyl silylchloride (MeSiCl, TMSCl) (19 μL, 16 mg, 0.15 mmol, 15 mol-%) in degassed anhydrous N,N-dimethylformamide (DMF) (3 mL). The zinc insertion product is prepared from tert-butyl(3S)-3-(tert-butoxycarbonylamino)-4-iodo-butanoate (6c) (385 mg, 1.0 mmol) in the presence of additional I2 (38 mg, 0.15 mmol, 15 mol-%) and TMSCl (19 μL, 16 mg, 0.15 mmol, 15 mol-%). Following the General Procedure of Description 15 (Part B), the zinc insertion product of (6c) is used in situ to cross couple with commercial 3-iodo-4-methyl-phenol (234 mg, 1.0 mmol) in the presence of tris(benzylideneacetone)dipalladium (Pd2(dba)3) (23 mg, 0.025 mmol, 2.5 mol-%) and tris(o-tolyl)phosphine (P(o-tol)3) (30 mg, 0.10 mmol, 10 mol-%) in anhydrous degassed DMF (3 mL). Filtration, aqueous work-up, and purification by silica gel column chromatography furnish the title compound (19a).

Workup

  1. customin anhydrous degassed DMF (3 mL)
  2. filtrationFiltration, aqueous work-up, and purification by silica gel column chromatography

Sources & evidence

ORD record
ord-dddb7151ad364b9d88a90dc24ee7bd6c
Source dataset
uspto-grants-2016_07
Patent number
US09394237B2

Reaction notes

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