Methanol → 4-{[N-(6-{[Bis(methylethyl)amino](2-cyanoethoxy)phosphinooxy}hexyl)carbamoyl]methyl)-2-oxo-2H-chromen-7-yl 2,2-dimethylpropanoate

HRID 2087118Notes

Reaction equation

HRID 2087118 reaction equation
[CH3:1][C:2]([CH3:29])([CH3:28])[C:3]([O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([CH2:17][C:18](=[O:27])[NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][OH:26])=[CH:11][C:12](=[O:16])[O:13]2)=[CH:8][CH:7]=1)=[O:4].C(N(CC)CC)C.[CH:37]([N:40]([CH:48]([CH3:50])[CH3:49])[P:41](Cl)[O:42][CH2:43][CH2:44][C:45]#[N:46])([CH3:39])[CH3:38].CO>C(Cl)Cl>[CH3:1][C:2]([CH3:29])([CH3:28])[C:3]([O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([CH2:17][C:18](=[O:27])[NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][O:26][P:41]([N:40]([CH:48]([CH3:50])[CH3:49])[CH:37]([CH3:38])[CH3:39])[O:42][CH2:43][CH2:44][C:45]#[N:46])=[CH:11][C:12](=[O:16])[O:13]2)=[CH:8][CH:7]=1)=[O:4]

Participants

6

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 27348442-Cyanoethyl N,N-diisopropylchlorophosphoramiditeHCID 226725124-{[N-(6-Hydroxyhexyl)carbamoyl]methyl}-2-oxo-2H-chromen-7-yl 2,2-dimethylpropanoate

Product 1

HCID 226725094-{[N-(6-{[Bis(methylethyl)amino](2-cyanoethoxy)phosphinooxy}hexyl)carbamoyl]methyl)-2-oxo-2H-chromen-7-yl 2,2-dimethylpropanoateYield 65.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 33a (0.6 g, 1.5 mmol) in 10 mL of anhydrous CH2Cl2 was added triethylamine (0.4 mL) followed by 2-cyanoethyl diisopropylchlorophosphoramidite (0.35 mL, 1.6 mmol). The solution was kept at room temperature for 1 h and treated with 0.1 mL of MeOH. The solvent was evaporated and the residue was partitioned between ethyl acetate and saturated NaHCO3. The organic phase was washed with saturated NaCl, dried over Na2SO4 and concentrated. The crude product was chromatographed on silica eluting with 5% triethylamine in ethyl acetate. Concentration of the pure product fractions and drying under vacuum afforded 0.59 g (65%) of 34 as a colorless, viscous oil.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between ethyl acetate and saturated NaHCO3
  3. washThe organic phase was washed with saturated NaCl
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was chromatographed on silica eluting with 5% triethylamine in ethyl acetate
  7. customConcentration of the pure product fractions and drying under vacuum

Sources & evidence

ORD record
ord-bdd28727ad2542e290ad6ea7d7d9b82b
Source dataset
uspto-grants-2004_04
Patent number
US06727356B1

Reaction notes

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