Ethyl Acetate → HCID 178437010, compound

HRID 1962870Notes

Reaction equation

HRID 1962870 reaction equation
[CH3:1]C(C)C(=O)C(P(=O)([O-])[O-])=[N+]=[N-].[C:13]([SiH2:17][O:18][C:19]([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:20]([NH:24][C:25](=[O:42])[CH:26]([O:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[N:36]=[CH:35][C:34]([C:40]#[CH:41])=[CH:33]2)[S:27][CH3:28])([CH3:23])[CH:21]=O)([CH3:16])([CH3:15])[CH3:14].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CO.[Cl-].[Na+].O>[C:13]([SiH2:17][O:18][C:19]([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:20]([NH:24][C:25](=[O:42])[CH:26]([O:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[N:36]=[CH:35][C:34]([C:40]#[CH:41])=[CH:33]2)[S:27][CH3:28])([CH3:23])[C:21]#[CH:1])([CH3:14])([CH3:15])[CH3:16]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 86586111Dimethyl-1-diazo-2-oxopropylphosphonateHCID 178437011HCID 178437011, compound

Product 1

HCID 178437010HCID 178437010, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of dimethyl-1-diazo-2-oxopropylphosphonate (0.86 g) in dry methanol (20 ml) was added at room temperature to a solution of crude N-[1-(tert-butyl-diphenyl-silanyloxymethyl)-1-methyl-2-oxo-ethyl]-2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-acetamide from Stage 3 in dry methanol (40 ml). The reaction medium was cooled down to 0° C. and potassium carbonate (0.773 g) was added portionwise along with additional dry methanol (10 ml). The reaction mixture was allowed to warm up to room temperature, stirred for 16 hours and then poured onto a mixture of ethyl acetate and brine. The two layers were separated and the aqueous layer was extracted thrice with ethyl acetate. The organic layers were combined, washed once with brine and then dried over sodium sulphate. After filtration and concentration under reduced pressure 1.84 g of crude mixture were isolated as a dark orange oil which was purified by flash chromatography on silica gel (hexane/ethyl acetate) to give the desired N-[1-(tert-butyl-diphenyl-silanyloxymethyl)-1-methyl-prop-2-ynyl]-2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-acetamide as a yellow oil (1.52 g). 1H NMR (CDCl3) δ ppm: 8.88 (1H, d); 8.19 (1H, d); 8.01 (1H, dd); 7.70-7.62 (4H, m); 7.46-7.30 (8H, m); 7.21-7.19, (1H, m); [{5.69 (s), 5.66 (s) 1H}, isomer A and isomer 13]; 3.93-3.72 (2H, dm); 3.30 (1H, s); 2.39 (1H, d); [{2.23 (s), 2.21 (s) 3H}, isomer A and isomer B]; 1.71 (3H, d); [{1.10 (s), 1.08 (s) 9H}, isomer A and isomer B].

Workup

  1. temperatureto warm up to room temperature
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted thrice with ethyl acetate
  4. washwashed once with brine
  5. dry with materialdried over sodium sulphate
  6. filtrationAfter filtration and concentration under reduced pressure 1.84 g of crude mixture
  7. customwere isolated as a dark orange oil which
  8. customwas purified by flash chromatography on silica gel (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c269fa9d716e4ccc95c2c82b9d10c2c9
Source dataset
uspto-grants-2013_04
Patent number
US08415272B2

Reaction notes

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