Hydrogen Peroxide → [(R)-1-Methyl-1-(3-oxo-1,5-dihydro-benzo[e][1,3,2]dioxaphosphepin-3-yloxymethyl)-3-(2-pentyl-benzoxazol-5-yl)-propyl]-carbamic acid tert-butyl ester

HRID 1170417Notes

Reaction equation

HRID 1170417 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][C@:8]([CH2:26][OH:27])([CH3:25])[CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]2[O:18][C:17]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[N:16][C:15]=2[CH:24]=1)([CH3:4])([CH3:3])[CH3:2].N1C=NN=N1.C(N(CC)[P:37]1[O:43][CH2:42][C:41]2[CH:44]=[CH:45][CH:46]=[CH:47][C:40]=2[CH2:39][O:38]1)C.OO.[O-:52]S([O-])(=S)=O.[Na+].[Na+]>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6](=[O:28])[NH:7][C@@:8]([CH3:25])([CH2:26][O:27][P:37]1(=[O:52])[O:38][CH2:39][C:40]2[CH:47]=[CH:46][CH:45]=[CH:44][C:41]=2[CH2:42][O:43]1)[CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]2[O:18][C:17]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[N:16][C:15]=2[CH:24]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 784Hydrogen PeroxideHCID 24477Sodium ThiosulfateHCID 41968792,4,3-Benzodioxaphosphepin-3-amine, N,N-diethyl-1,5-dihydro-HCID 68767645[(R)-1-Hydroxymethyl-1-methyl-3-(2-pentyl-benzoxazol-5-yl)-propyl]-carbamic acid tert-butyl esterHCID 178418441HCID 178418441, compound

Product 1

HCID 68770694[(R)-1-Methyl-1-(3-oxo-1,5-dihydro-benzo[e][1,3,2]dioxaphosphepin-3-yloxymethyl)-3-(2-pentyl-benzoxazol-5-yl)-propyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under an atmosphere of argon a solution of [(R)-1-Hydroxymethyl-1-methyl-3-(2-pentyl-benzoxazol-5-yl)-propyl]-carbamic acid tert-butyl ester (151 mg, 0.387 mmol) and tetrazole (85 mg, 1.21 mmol) in dry THF (3 ml) was treated with N,N-diethyl-1,5-dihydro-2,4,3-benzo-dioxaphosphepin-3-amine (185 mg, 0.77 mmol) and stirred for 1 hours at RT. After cooling the reaction mixture to 0° C., aqueous hydrogen peroxide (0.4 ml of a 30 w/w % solution) was added and the reaction was allowed to stir for one hour at RT. The reaction mixture was distributed between a 10% aqueous Na2S2O3 solution and AcOEt. The organic layer was dried over MgSO4, concentrated in vacuum and purified over silica gel (eluent (DCM/methanol 30/1). The title compound was obtained as an colorless amorphous solid. 1H-NMR (DMSO-d6) δ: 7.52 (d, J=8.3 Hz; 1H), 7.50-7.40 (m; 5H), 7.15 (dd, J=8.3, 1.5 Hz; 1H), 6.8 (bs; 1H), 5.32-5.26/5.16-5.04 (m; 4H), 4.17/4.06 (AB-system, J=9.5, 4.5 Hz; 2H), 2.88 (t, J=7.5 Hz; 2H), 2.71-2.58 (m; 2H), 2.14-2.08 (m; 1H), 1.81-1.68 (m; 3H), 1.38 (s; 9H); 1.28 (s; 3H), 1.38-1.28 (m; 4H), 0.85 (m; 3H).

Workup

  1. temperatureAfter cooling the reaction mixture to 0° C.
  2. stirringto stir for one hour at RT
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated in vacuum
  5. custompurified over silica gel (eluent (DCM/methanol 30/1)

Sources & evidence

ORD record
ord-d14a4e90f0154af6a247c7c29718c810
Source dataset
uspto-grants-2010_11
Patent number
US07825260B2

Reaction notes

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