m-Chloroperbenzoic acid → HCID 67374942, compound

HRID 1805915Notes

Reaction equation

HRID 1805915 reaction equation
C(N(C(C)C)[P:5]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(C)C.N1C=NN=N1.[C:30]([O:33][C:34]1[C:43]([CH3:44])=[CH:42][C:41]([CH2:45][CH2:46][CH2:47][OH:48])=[CH:40][C:35]=1[C:36]([O:38][CH3:39])=[O:37])(=[O:32])[CH3:31].ClC1C=C(C=CC=1)C(OO)=[O:54]>C(Cl)Cl.CCOC(C)=O>[C:30]([O:33][C:34]1[C:43]([CH3:44])=[CH:42][C:41]([CH2:45][CH2:46][CH2:47][O:48][P:5]([O:6][CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:54])=[CH:40][C:35]=1[C:36]([O:38][CH3:39])=[O:37])(=[O:32])[CH3:31]

Participants

7

Reactant 4

HCID 70297m-Chloroperbenzoic acid2×HCID 196621Bis(benzyloxy)(diisopropylamino)phosphine2×HCID 67379178HCID 67379178, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 67374942HCID 67374942, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

Dibenzyl N,N-diisopropylphosphoramidite (0.252 mL, 0.751 mmol) was added to a stirred solution of 1H-tetrazole (3 wt % in CH3CN) (4.40 mL, 1.502 mmol) and methyl 2-(acetyloxy)-5-(3-hydroxypropyl)-3-methylbenzoate (100 mg, 0.376 mmol) in dry CH2Cl2 (4.50 mL) at 25° C. under N2. The reaction was stirred for 2 h at 25° C. After this time another 0.5 eq dibenzyl N,N-diisopropylphosphoramidite was added and the reaction was stirred for 30 min. The reaction mixture was cooled to 0° C. and a solution of 3-chloroperoxybenzoic acid (337 mg, 1.502 mmol) in dry CH2Cl2 (3.00 mL) was added via cannula. After 30 min another 1 eq 3-chloroperoxybenzoic acid was added and the reaction was stirred at 0° C. After 30 min the reaction was diluted with EtOAc (30 mL) and washed with successive portions of saturated Na2SO3 (20 mL) and saturated NaHCO3 (20 mL), dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 144 mL, gradient to 60% EtOAc in hexanes over 2394 mL) to afford methyl 2-(acetyloxy)-5-(3-{[bis(benzyloxy)phosphoryl]oxy}propyl)-3-methylbenzoate, as a colorless oil. LCMS calc.=527.2; found=527.0 (M+H)+. 1H NMR (500 MHz, CHCl3): δ 7.62 (d, J=2.2 Hz, 1 H); 7.36-7.31 (m, 10 H); 7.18 (d, J=2.2 Hz, 1 H); 5.11-4.98 (m, 4 H); 4.00 (q, J=6.6 Hz, 2 H); 3.84 (s, 3 H); 2.61 (t, J=7.8 Hz, 2 H); 2.36 (s, 3 H); 2.17 (s, 3 H); 1.93-1.85 (m, 2 H).

Workup

  1. stirringthe reaction was stirred for 30 min
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. stirringthe reaction was stirred at 0° C
  4. washwashed with successive portions of saturated Na2SO3 (20 mL) and saturated NaHCO3 (20 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give the crude product
  8. customThis was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 144 mL, gradient to 60% EtOAc in hexanes over 2394 mL)

Sources & evidence

ORD record
ord-1f5b68756e124c7e98515819fdf8cbe3
Source dataset
uspto-grants-2013_01
Patent number
US08354454B2

Reaction notes

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