Isopropanol → 2'-[(t-Butoxycarbonylamino)methyl]-4-[(t-butyldiphenylsiloxy)methyl]-1,1'-biphenyl

HRID 1740223Notes

Reaction equation

HRID 1740223 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].C(O)(C)C.[C:35]([O:39][C:40]([NH:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1Br)=[O:41])([CH3:38])([CH3:37])[CH3:36]>C1C=CC=CC=1.O.[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:35]([O:39][C:40]([NH:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[C:23]1[CH:24]=[CH:25][C:20]([CH2:19][O:18][Si:1]([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:21][CH:22]=1)=[O:41])([CH3:38])([CH3:36])[CH3:37]

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 14798Sodium HydroxideHCID 70183002-Bromo-N-(tert-butoxycarbonyl)benzylamineHCID 15224568(4-(((tert-Butyldiphenylsilyl)oxy)methyl)phenyl)boronic acid

Product 1

HCID 220084542'-[(t-Butoxycarbonylamino)methyl]-4-[(t-butyldiphenylsiloxy)methyl]-1,1'-biphenylYield 100%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 241BenzeneSolventHCID 962WaterSolvent2×

Procedure

To a solution of 3.2 g (8.2 mmol) of 4-(t-butyldiphenylsilyoxymethyl)phenylboronic acid (Step C) in 64 mL of benzene was added 2.2 mL of water, 6.4 mL of 5N aqueous sodium hydroxide, and 8.3 mL of isopropanol. To this mixture was added 180 mg (0.16 mmol) of tetrakis(triphenylphosphine) palladium and 2.20 g (7.81 mmol) of N-(t-butoxycarbonyl)-2-bromobenzylamine (Step D). The resulting mixture was heated under nitrogen at reflux for 2 hours then cooled to room temperature. The reaction mixture was diluted with 100 mL of water, transferred to a separatory funnel and extracted with ether (3×150 mL). The combined ether extracts were washed with saturated aqueous sodium bicarbonate (100 mL) and saturated aqueous sodium chloride (100 mL), dried over magnesium sulfate and 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 (9:1) to afford 4.31 g (100%) of the product as a clear oil. 1H NMR (200 MHz, CDCl3): δ 1.11 (s, 9H), 1.41 (s, 9H), 4.27 (d, 6 Hz, 2H), 4.45 (m, 1H), 4.81 (s, 2H), 7.20-7.49 (m, 14H), 8.72 (m, 4H). FAB-MS: calculated for C35H41NO3Si 551; found 552 (M+H).

Workup

  1. temperatureThe resulting mixture was heated under nitrogen
  2. temperatureat reflux for 2 hours
  3. customtransferred to a separatory funnel
  4. extractionextracted with ether (3×150 mL)
  5. washThe combined ether extracts were washed with saturated aqueous sodium bicarbonate (100 mL) and saturated aqueous sodium chloride (100 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customThe solvent was removed under vacuum
  9. customto give a crude product which
  10. customwas purified by column chromatography on silica gel eluting with hexanes/ethyl acetate (9:1)

Sources & evidence

ORD record
ord-c9dbeecd24e446f484459fa7c91375ad
Source dataset
uspto-grants-1999_10
Patent number
US05968924

Reaction notes

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