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

HRID 1866499Notes

Reaction equation

HRID 1866499 reaction equation
[CH3:1][O:2][C:3](=[O:41])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][C@H:12]([NH:14][CH2:15][C@H:16]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[C:17]2[CH:22]=[CH:21][C:20]([O:23]CC3C=CC=CC=3)=[C:19]([CH2:31][OH:32])[CH:18]=2)[CH3:13])[CH:6]=1>[Pd].C(O)C>[NH3:14].[CH3:1][O:2][C:3](=[O:41])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][C@H:12]([NH:14][CH2:15][C@H:16]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:35])[CH3:36])[C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([CH2:31][OH:32])[CH:18]=2)[CH3:13])[CH:6]=1

Participants

5

Reactant 1

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

Product 2

HCID 222AmmoniaHCID 58959781methyl (3-{(2R)-2-[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetateYield 89.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A suspension of methyl(3-{(2R)-2-[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-[benzyloxy]-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetate (Preparation 22) (5.27 g, 9.12 mmol) and 10% palladium on carbon (1.00 g) in ethanol (50 ml) was stirred under an atmosphere of hydrogen (60 psi) at room temperature for 16 hours. The catalyst was filtered off through arbocel and the filtrate concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (96:4:0.4 changing to 95:5:0.5, by volume) to give the title compound as a pale yellow oil (1.99 g) which was used without further purification. 1H NMR (400 MHz, CD3OD): δ=7.21-7.17 (2H, m), 7.11-7.09 (1H, d), 7.03-6.98 (3H, m), 6.69-6.67 (1H, d), 4.71-4.68 (1H, t), 4.62-4.61 (2H, d), 3.67 (3H, s), 3.59 (2H, s), 2.96-2.86 (2H, m), 2.69-2.55 (3H, m), 1.07-1.05 (3H, d), 0.82 (9H, s), −0.01 (3H, s), −0.20 (3H, s) ppm. LRMS (electrospray): m/z [M+H]+ 488, [M+Na]+ 510, [M−H]− 486.

Workup

  1. filtrationThe catalyst was filtered off through arbocel
  2. concentrationthe filtrate concentrated in vacuo
  3. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-4c19d6a83cc1459e86b9bc633e15fd69
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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