Methanol → HCID 18551506, compound

HRID 1250795Notes

Reaction equation

HRID 1250795 reaction equation
[CH:1]([N:4]([CH:12]([CH3:14])[CH3:13])[P:5](Cl)[O:6][CH2:7][CH2:8][C:9]#[N:10])([CH3:3])[CH3:2].[C:15]([O:18][CH:19]([O:58][C:59](=[O:61])[CH3:60])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH:31]([OH:57])[CH2:32][O:33][C:34]([C:49]2[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][CH:50]=2)([C:41]2[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:22][CH:21]=1)(=[O:17])[CH3:16].CO.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C.CCCCCC>[C:15]([O:18][CH:19]([O:58][C:59](=[O:61])[CH3:60])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH:31]([O:57][P:5]([N:4]([CH:12]([CH3:14])[CH3:13])[CH:1]([CH3:3])[CH3:2])[O:6][CH2:7][CH2:8][C:9]#[N:10])[CH2:32][O:33][C:34]([C:41]2[CH:42]=[CH:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=2)([C:49]2[CH:50]=[CH:51][C:52]([O:55][CH3:56])=[CH:53][CH:54]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:22][CH:21]=1)(=[O:17])[CH3:16]

Participants

8

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 27348442-Cyanoethyl N,N-diisopropylchlorophosphoramiditeHCID 70010871HCID 70010871, compound

Product 1

HCID 18551506HCID 18551506, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 81531DiisopropylethylamineSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
25 °C

Procedure

2-Cyanoethyl diisopropylchlorophosphoramidite (0.49 ml, 2.19 mmol) was added to a solution of 9 (0.83 g, 1.29 mmol) dissolved in 32 ml of anhydrous methylene chloride containing 0.67 ml of N,N-diisopropylethylamine. The reaction solution was stirred for 1.0 h at 25° C. under argon and then treated with 1.0 ml of methanol and poured into 300 ml of 5% sodium bicarbonate solution. The mixture was extracted with ethyl acetate (300 ml) and the extract was dried over sodium sulfate and evaporated. The crude product was purified by silica gel chromatography eluting with a gradient of 25-50% ethyl acetate in hexane (2% triethylamine). The pure phosphoramidite fractions were evaporated affording a homogenous oil: 0.61 g (56%) yield; TLC (1:1, ethyl acetate/hexane), Rf=0.62; 31P NMR (DMSO-d6) 147.82 (singlet). Anal. Calcd for C47H59N2O10P.0.2H2O: C, 66.68; H, 7.07; N, 3.31. Found: C, 66.46; H, 7.27; N, 2.94.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (300 ml)
  2. dry with materialthe extract was dried over sodium sulfate
  3. customevaporated
  4. customThe crude product was purified by silica gel chromatography
  5. washeluting with a gradient of 25-50% ethyl acetate in hexane (2% triethylamine)
  6. customThe pure phosphoramidite fractions were evaporated
  7. customaffording a homogenous oil
  8. custom0.61 g (56%) yield

Sources & evidence

ORD record
ord-60f86df2a5ee4e039261d0b7504c187b
Source dataset
uspto-grants-2002_01
Patent number
US06339147B1

Reaction notes

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