2-Bromo-N-(tert-butoxycarbonyl)benzylamine → 2'-[(t-Butoxycarbonylamino)methyl]-4-[(t-butyldimethylsiloxy)-methyl]-1,1'-biphenyl

HRID 1080743Notes

Reaction equation

HRID 1080743 reaction equation
[O:1]([CH2:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1)[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].O.O.O.O.O.O.[OH-].[Ba+2].[OH-].[C:28]([O:32][C:33]([NH:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1Br)=[O:34])([CH3:31])([CH3:30])[CH3:29]>COCCOC.[Cl-].[NH4+].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:28]([O:32][C:33]([NH:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:1][Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3])=[CH:11][CH:12]=1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

7

Reactant 3

HCID 70183002-Bromo-N-(tert-butoxycarbonyl)benzylamineHCID 233654354-(tert-Butyldimethylsilyloxymethyl)phenylboronic acidHCID 129776469Barium(2+);dihydroxide;hexahydrate

Product 1

HCID 233654482'-[(t-Butoxycarbonylamino)methyl]-4-[(t-butyldimethylsiloxy)-methyl]-1,1'-biphenylYield 75.1%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1.0 g (3.8 mmol) of 4-(t-butyldimethaylsilyoxymethyl)phenylboronic acid (Step E) in 24 mL of 1,2-dimethyoxyethane was added 4 mL of water,m 1.02 g (5.37 mmol) of barium hydroxide hexahydrate, 1.02 g (3.58 mmol) of N-(t-butoxycarbonyl)-2-bromobenzylamine (Step F) and 206 mg (0.18 mmol) of tetrakis(triphenylphosphine) palladium. The resulting mixture was heated under nitrogen at 80° C. for 2.5 hours then cooled to room temperature. The reaction mixture was diluted with 40 mL of saturated aqueous ammonium chloride. The solution was transferred to a separatory funnel and extracted with ether (3×75 mL). The combined ether extracts were washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over magnesium sulfate and then filtered. The solvent was removed under vacuum to give a crude product which was purified by column chromatography on silica gel eluting with hexanes/ethyl acetate (85:15) to afford 1.15 g (75%) of the product as a clear oil. FAB-MS: calculated for C25H37NO3Si 427; found 314. 1H NMR (200 MHz, CDCl3): 0.10 (s, 6H), 0.92 (s, 9H), 1.40 (s, 9H), 4.27 (d, 5 Hz, 2H), 4.60 (s, 1H), 4.78 (s, 2H), 7.18-7.45 (m, 8H).

Workup

  1. temperaturethen cooled to room temperature
  2. customThe solution was transferred to a separatory funnel
  3. extractionextracted with ether (3×75 mL)
  4. washThe combined ether extracts were washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed under vacuum
  8. customto give a crude product which
  9. customwas purified by column chromatography on silica gel eluting with hexanes/ethyl acetate (85:15)

Sources & evidence

ORD record
ord-09a9b8dc0e6b45d6a534e1bf219e9130
Source dataset
uspto-grants-1996_12
Patent number
US05583130

Reaction notes

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