Methanol → HCID 22672509, compound

HRID 481181Notes

Reaction equation

HRID 481181 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 22672509HCID 22672509, compoundYield 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 34a 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-b52243ae177243ae8696721998d119d5
Source dataset
uspto-grants-2003_11
Patent number
US06653473B2

Reaction notes

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