m-Chloroperbenzoic acid → [(S)-2-((R)-8-Hydroxymethyl-7,8-dihydro-[1,4]dioxino[2,3-g]indazol-1-yl)-1-methyl-ethyl]-carbamic acid benzyl ester

HRID 31364Notes

Reaction equation

HRID 31364 reaction equation
[CH2:1]([O:8][C:9](=[O:30])[NH:10][C@@H:11]([CH3:29])[CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([O:24][CH2:25][C@@H:26]3C[O:27]3)[C:20]=2C=O)[CH:15]=[N:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C=CC=C([C:38](OO)=[O:39])C=1.CC(C)=O.ClCCl>ClCCl>[CH2:1]([O:8][C:9](=[O:30])[NH:10][C@@H:11]([CH3:29])[CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]3[O:24][CH2:25][C@@H:26]([CH2:38][OH:39])[O:27][C:20]3=2)[CH:15]=[N:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 70297m-Chloroperbenzoic acidHCID 21584124Propan-2-one--dichloromethane (1/1)HCID 86605340HCID 86605340, compound

Product 1

HCID 69253308[(S)-2-((R)-8-Hydroxymethyl-7,8-dihydro-[1,4]dioxino[2,3-g]indazol-1-yl)-1-methyl-ethyl]-carbamic acid benzyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of the epoxide from Step A (0.86 g, 2.10 mmol) in dichloromethane (100 mL) was added m-chloroperbenzoic acid (70%, 0.62 g, 2.52 mmol) in portions under nitrogen atmosphere. After the addition completed the reaction mixture was stirred overnight. The reaction was quenched by a saturated aqueous solution of sodium thiosulfate (20 mL) and dichloromethane was evaporated. To the aqueous residue was added potassium carbonate (1.0 g) and methanol (200 mL), the resulting mixture was stirred for ½ h and organic solvent was evaporated. The residue was extracted with ethyl acetate (50 mL×3), dried and evaporated to dryness to afford an oil. Chromatography on silica eluting with a gradient of 0% to 10% acetone/dichloromethane gave an oil (0.50 g, 60%). LCMS (+APCI) m/z 397 (M+H), 1H NMR (600 MHz, CDCl3) δ 7.82 (s, 1H), 7.33-7.13 (m, 5H), 7.14 (d, J=8.4 Hz, 1H), 6.74 (d, J=8.4 Hz, 1H), 5.04-4.97 (m, 3H), 4.65 (ddd, J=6.6, 13.4, 51.6 Hz, 2H), 4.32 (m, 3H), 4.08 (m, 2H), 3.91 (m, 2H), 1.18(d, J=7.2 Hz, 3H).

Workup

  1. additionAfter the addition
  2. customThe reaction was quenched by a saturated aqueous solution of sodium thiosulfate (20 mL) and dichloromethane
  3. customwas evaporated
  4. additionTo the aqueous residue was added potassium carbonate (1.0 g) and methanol (200 mL)
  5. stirringthe resulting mixture was stirred for ½ h
  6. customorganic solvent was evaporated
  7. extractionThe residue was extracted with ethyl acetate (50 mL×3)
  8. customdried
  9. customevaporated to dryness
  10. customto afford an oil

Sources & evidence

ORD record
ord-943c211582a540b09768b8a508341c3e
Source dataset
uspto-grants-2008_09
Patent number
US07425572B2

Reaction notes

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