[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanol → methyl(3-{(2R)-2-[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-[benzyloxy]-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetate

HRID 1866500Notes

Reaction equation

HRID 1866500 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.[NH2:28][C@H:29]([CH3:42])[CH2:30][C:31]1[CH:32]=[C:33]([CH2:37][C:38]([O:40][CH3:41])=[O:39])[CH:34]=[CH:35][CH:36]=1>ClCCl>[NH3:28].[CH3:41][O:40][C:38](=[O:39])[CH2:37][C:33]1[CH:34]=[CH:35][CH:36]=[C:31]([CH2:30][C@H:29]([NH:28][CH2:16][C@H:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[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)[CH3:42])[CH:32]=1

Participants

5

Reactant 2

HCID 12988834[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanolHCID 46938716Methyl {3-[(2R)-2-aminopropyl]phenyl}acetate

Product 2

HCID 222AmmoniaHCID 57978350methyl(3-{(2R)-2-[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-[benzyloxy]-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetateYield 75.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of [2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanol (Preparation 23) (12.5 g, 27.7 mmol) and methyl {3-[(2R)-2-aminopropyl]phenyl}acetate (Preparation 25) (11.5 g, 55.4 mmol) in dichloromethane (130 ml) was heated to 90° C., allowing the dichloromethane to evaporate. The resulting melt was left at 90° C. for a further 16 hours. The reaction mixture was cooled to room temperature and purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (98:2:0.2 changing to 97:3:0.3, by volume) to give the title compound (12.1 g) as a white oil. 1H NMR (400 MHz, CD3OD): δ=7.47-7.45 (2H, m), 7.39-7.29 (4H, m), 7.19-7.15 (1H, t), 7.13-7.07 (2H, m), 7.03 (1H, s), 7.01-6.99 (1H, d), 6.93-6.91 (1H, d), 5.12 (2H, s), 4.76-4.73 (1H, t), 4.67-4.66 (2H, d), 3.66 (3H, s), 3.58 (2H, s), 2.95-2.80 (2H, m), 2.68-2.55 (3H, m), 1.06-1.05 (3H, d), 0.83 (9H, s), 0.00 (3H, s), −0.19 (3H, s) ppm. LRMS (electrospray): m/z [M+H]+ 578, [M+Na]+ 600.

Workup

  1. customto evaporate
  2. custompurified by flash column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-cc91d98e5afd48fcbab58c54ffcb75ad
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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