4-tert-Butylphenyl glycidyl ether, (+)- → 1'-[(2S)-3-(4-tert-butylphenoxy)-2-hydroxypropyl]spiro[naphtho[1,2-b][1,4]oxathiine-2,4'-piperidine]-5,6-dione

HRID 1665415Notes

Reaction equation

HRID 1665415 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4]2([O:11][C:10]3[C:12]4[C:17]([C:18](=[O:21])[C:19](=[O:20])[C:9]=3[S:8][CH2:7]2)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:3][CH2:2]1.[C:22]([C:26]1[CH:36]=[CH:35][C:29]([O:30][CH2:31][C@@H:32]2[CH2:34][O:33]2)=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23]>C(O)C>[C:22]([C:26]1[CH:36]=[CH:35][C:29]([O:30][CH2:31][C@@H:32]([OH:33])[CH2:34][N:1]2[CH2:2][CH2:3][C:4]3([O:11][C:10]4[C:12]5[C:17]([C:18](=[O:21])[C:19](=[O:20])[C:9]=4[S:8][CH2:7]3)=[CH:16][CH:15]=[CH:14][CH:13]=5)[CH2:5][CH2:6]2)=[CH:28][CH:27]=1)([CH3:23])([CH3:24])[CH3:25]

Participants

4

Reactant 2

HCID 7193734-tert-Butylphenyl glycidyl ether, (+)-HCID 57661820Spiro[naphtho[1,2-b][1,4]oxathiine-2,4'-piperidine]-5,6-dione

Product 1

HCID 236245911'-[(2S)-3-(4-tert-butylphenoxy)-2-hydroxypropyl]spiro[naphtho[1,2-b][1,4]oxathiine-2,4'-piperidine]-5,6-dioneYield 49%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of spiro[naphtho[1,2-b][1,4]oxathiine-2,4′-piperidine]-5,6-dione (10.0 g, 33.18 mmol) in absolute ethanol (100 mL) was added (2S)-2-[(4-tert-butylphenoxy)methyl]oxirane (8.9 g, 43.14 mmol). The reaction mixture was stirred at 90° C. for 15 h (sometimes the reaction is complete within 2-3 hours). The reaction mixture was cooled to room temperature the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography (SiO2, 10% EtOAc in dichloromethane to 50% EtOAc in dichloromethane) to give the desired product as a purple solid (8.1 g, 49%). M.p.=155-157° C.; 400 MHz 1H NMR (CDCl3) δ: 8.1-8.03 (m, 1H), 7.8-7.74 (m, 1H), 7.7-7.6 (m, 1H), 7.55-7.45 (m, 1H), 7.35-7.28 (m, 2H), 6.9-6.8 (m, 2H), 4.10-4.17 (m, 1H), 4.0-3.93 (m, 2H), 2.99-2.95 (s, 3H), 2.86-2.74 (m, 2H), 2.7-2.64 (m, 2H), 2.6-2.51 (m, 1H), 2.22-2.13 (m, 2H), 1.98-1.84 (m, 2H), 1.3 (s, 9H); LCMS: 508 [M+H]; enantiomeric excess determined from chiral HPLC: 98%; Chiral HPLC Rt=50.98 min

Workup

  1. waitis complete within 2-3 hours
  2. temperatureThe reaction mixture was cooled to room temperature the solvent
  3. customwas removed under reduced pressure
  4. customThe crude product was purified by flash column chromatography (SiO2, 10% EtOAc in dichloromethane to 50% EtOAc in dichloromethane)

Sources & evidence

ORD record
ord-19f26a47ce6f4c4c9394f5b38589b234
Source dataset
uspto-grants-2011_10
Patent number
US08039503B2

Reaction notes

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