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

HRID 322038Notes

Reaction equation

HRID 322038 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 separators 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 hexaneslethyl acetate (9:1) to afford 4.31 g (100%) of the product as a clear oil. 1H NMR (200 MHz, CDCl3): d 1.11 (s, 9 H), 1.41 (s, 9 H), 4.27 (d, 6 Hz, 2 H), 4.45 (m, 1 H), 4.81 (s, 2 H), 7.20-7.49 (m, 14 H), 8.72 (m, 4 H). 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 separators 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 hexaneslethyl acetate (9:1)

Sources & evidence

ORD record
ord-a6a21313568d4f58a166c8e96c7f99f6
Source dataset
uspto-grants-2001_04
Patent number
US06211174B1

Reaction notes

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