[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanol → Ammonia

HRID 1866551Notes

Reaction equation

HRID 1866551 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:16]Br)=[CH:11][C:10]=1[CH2:26][OH:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28]([O:35][C:36](=[O:50])[CH:37]=[CH:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][C:46]([NH2:49])([CH3:48])[CH3:47])[CH:40]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(OCC)C>[NH3:49].[CH2:28]([O:35][C:36](=[O:50])[CH:37]=[CH:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][C:46]([NH:49][CH2:16][C@@H:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[C:10]([CH2:26][OH:27])[CH:11]=2)[O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])([CH3:47])[CH3:48])[CH:40]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

5

Reactant 2

HCID 12988834[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanolHCID 690261303-[3-(2-Amino-2-methyl-propyl)phenyl]-acrylic acid benzyl ester

Product 2

HCID 222AmmoniaHCID 69024828Benzyl-3-(3-{2-[((2R)-2-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]-2-methyl propyl}phenyl)acrylate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of [2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl) phenyl]methanol (Preparation 23) (800 mg, 1.77 mmol) and 3-[3-(2-amino-2-methyl-propyl)phenyl]-acrylic acid benzyl ester (preparation 142), (1.10 g, 3.55 mmol) was stirred at 90° C. for 18 hours. The reaction mixture was then cooled to room temperature, diluted with diethyl ether (40 mL) and stirred for 4 hours. The resulting precipitate was filtered off, washing though with diethyl ether, and the filtrate was concentrated in vacuo to give a brown oil. Purification of the oil by column chromatography on silica gel, eluting with dichloromethane:methanol:0.88 ammonia afforded the title compound in 25% yield, 300 mg. 1H NMR (400 MHz, CD3OD) δ: 7.78 (1H, d), 7.38 (16H, m), 6.95 (1H, m), 6.58 (1H, d), 5.25 (2H, s), 5.04 (2H, s), 4.78 (1H, m), 4.64 (2H, m), 2.80 (2H, m), 2.68 (2H, m), 1.14 (3H, s), 1.10 (3H, s), 0.78 (9H, s), −0.03 (3H, s), −0.21 (3H, s) ppm; LRMS ESI m/z 680 [M+H]+

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. stirringstirred for 4 hours
  3. filtrationThe resulting precipitate was filtered off
  4. washwashing though with diethyl ether
  5. concentrationthe filtrate was concentrated in vacuo
  6. customto give a brown oil
  7. customPurification of the oil by column chromatography on silica gel
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-47a53522ff1b470eaad684cd2a4ddbc0
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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