(S,E)-(2-((tert-butyldimethylsilyloxy)methyl)-4-(prop-1-enyl)-2,3-dihydro-1H-pyrrol-1-yl)(5-methoxy-2-nitro-4-(triisopropylsilyloxy)phenyl)methanone → (S,E)-(2-amino-5-methoxy-4-(triisopropylsilyloxy)phenyl)(2-((tert-butyldimethylsilyloxy)methyl)-4-(prop-1-enyl)-2,3-dihydro-1H-pyrrol-1-yl)methanone

HRID 513358Notes

Reaction equation

HRID 513358 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]1[CH2:14][C:13](/[CH:15]=[CH:16]/[CH3:17])=[CH:12][N:11]1[C:18]([C:20]1[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][Si:29]([CH:36]([CH3:38])[CH3:37])([CH:33]([CH3:35])[CH3:34])[CH:30]([CH3:32])[CH3:31])=[CH:22][C:21]=1[N+:39]([O-])=O)=[O:19])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>[Zn].C(O)=O.C(O)C>[NH2:39][C:21]1[CH:22]=[C:23]([O:28][Si:29]([CH:33]([CH3:34])[CH3:35])([CH:36]([CH3:38])[CH3:37])[CH:30]([CH3:32])[CH3:31])[C:24]([O:26][CH3:27])=[CH:25][C:20]=1[C:18]([N:11]1[CH:12]=[C:13](/[CH:15]=[CH:16]/[CH3:17])[CH2:14][C@H:10]1[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3])=[O:19]

Participants

4

Reactant 1

HCID 86717761(S,E)-(2-((tert-butyldimethylsilyloxy)methyl)-4-(prop-1-enyl)-2,3-dihydro-1H-pyrrol-1-yl)(5-methoxy-2-nitro-4-(triisopropylsilyloxy)phenyl)methanone

Product 1

HCID 86717762(S,E)-(2-amino-5-methoxy-4-(triisopropylsilyloxy)phenyl)(2-((tert-butyldimethylsilyloxy)methyl)-4-(prop-1-enyl)-2,3-dihydro-1H-pyrrol-1-yl)methanoneYield 69%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 23437341Formic acid ethanolSolvent

Conditions

Temperature
27.5 °C

Procedure

Zinc dust (22.0 g, 0.33 mol, 37 eq) was added, in portions over 20 mins, to a solution of the propenyl intermediate 6 (5.5 g, 9.1 mmol, 1.0 eq) in 5% v/v formic acid/ethanol (55 mL), using an ice bath to maintain the temperature between 25-30° C. After 30 mins, the reaction mixture was filtered through a short bed of Celite®. The Celite® was washed with ethyl acetate (65 mL) and the combined organics were washed successively with water (35 mL), saturated sodium bicarbonate (35 mL) and brine (10 mL). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, 90/10 v/v n-hexane/EtOAc) to afford the product as a pale yellow oil (3.6 g, 69.0%). LC/MS (4.439 min (ES+)), m/z: 575.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 6.75 (m, 1H), 6.40 (br s, 1H), 6.28 (m, 1H), 6.11 (d, 1H, J=15.4 Hz), 5.53 (m, 1H), 4.67 (m, 1H), 4.36 (m, 2H), 3.93 (br s, 1H), 3.84 (br s, 1H), 3.73 (s, 3H), 2.86 (dd, 1H, J=15.7, 10.4 Hz), 2.73 (dd, 1H, J=15.9, 4.5 Hz), 1.80 (dd, 3H, J=6.8, 1.3 Hz), 1.35-1.23 (m, 3H), 1.12 (d, 18H, J=7.3 Hz), 0.89 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H).

Workup

  1. filtrationthe reaction mixture was filtered through a short bed of Celite®
  2. washThe Celite® was washed with ethyl acetate (65 mL)
  3. washthe combined organics were washed successively with water (35 mL), saturated sodium bicarbonate (35 mL) and brine (10 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (silica gel, 90/10 v/v n-hexane/EtOAc)

Sources & evidence

ORD record
ord-41e6412a56984bbcb2e65398b6d6a882
Source dataset
uspto-grants-2015_08
Patent number
US09102704B2

Reaction notes

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