1,4-Dioxane → tert-Butyl 5-(6-(3-(benzyloxy)phenylthio)-1,2,3,4-tetrahydronaphthalen-2-yl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamate

HRID 1802135Notes

Reaction equation

HRID 1802135 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([CH:17]2[CH2:26][CH2:25][C:24]3[CH:23]=[C:22](OS(C(F)(F)F)(=O)=O)[CH:21]=[CH:20][C:19]=3[CH2:18]2)[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:35]([O:42][C:43]1[CH:44]=[C:45]([SH:49])[CH:46]=[CH:47][CH:48]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.O1CCOCC1.C(N(CC)C(C)C)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCOC(C)=O.CCCCCC>[CH2:35]([O:42][C:43]1[CH:44]=[C:45]([S:49][C:22]2[CH:23]=[C:24]3[C:19](=[CH:20][CH:21]=2)[CH2:18][CH:17]([C:9]2([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11][CH2:10]2)[CH2:26][CH2:25]3)[CH:46]=[CH:47][CH:48]=1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

9

Reactant 5

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 249006013-(Benzyloxy)benzene-1-thiolHCID 86642939Trifluoromethanesulfonic acid 6-(5-tert-butoxycarbonylamino-2,2-dimethyl-1,3-dioxinan-5-yl)-5,6,7,8-tetrahydro-naphthalen-2-yl ester

Product 1

HCID 86642938tert-Butyl 5-(6-(3-(benzyloxy)phenylthio)-1,2,3,4-tetrahydronaphthalen-2-yl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamateYield 69.4%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

Trifluoromethanesulfonic acid 6-(5-tert-butoxycarbonylamino-2,2-dimethyl-1,3-dioxinan-5-yl)-5,6,7,8-tetrahydro-naphthalen-2-yl ester (0.310 g, 0.000608 mol), 3-benzyloxy-benzenethiol (0.145 g, 0.000669 mol), tris(dibenzylideneacetone)-dipalladium(0) (0.0167 g, 0.0000182 mol) and xantphos (0.0211 g, 0.0000365 mol) were dissolved in 1,4-dioxane (10 mL, 0.1 mol). The solution was degassed by applying low vacuum and backfilling with N2 for 5 times. The pre-degassed N,N-diisopropylethylamine (0.350 mL, 0.00201 mol) in the same way was added. The mixture was heated to reflux under an atmosphere of nitrogen for 14 hours then cooled to r.t. tris(dibenzylideneacetone)dipalladium(0) (0.0501 g, 0.0000548 mol) and xantphos (0.0634 g, 0.000110 mol) was added. The mixture was degassed three times, heated to reflux for 6 more hours, cooled to r.t. The mixture was filtered, and concentrated to give a crude residue. Chromatography with EtOAc-hexane (0:100 to 20:80) two times gave a solid product (243 mg, 43%). 1H NMR (CHLOROFORM-d) δ: 7.31-7.44 (m, 5H), 7.18-7.23 (m, 1H), 7.17 (d, J=2.0 Hz, 2H), 7.04-7.09 (m, 1H), 6.97-7.04 (m, 1H), 6.84-6.92 (m, 1H), 6.79-6.84 (m, 1H), 5.02 (s, 2H), 4.86 (s, br, 1H), 3.95-4.05 (m, 4H), 2.77-2.97 (m, 4H), 2.64-2.76 (m, 1H), 2.47-2.60 (m, 1H), 2.00-2.14 (m, 1H), 1.51-1.60 (m, 6H), 1.41-1.51 (m, 9H). MS (M+Na+): 598.0.

Workup

  1. customThe solution was degassed
  2. temperatureThe mixture was heated
  3. temperatureto reflux under an atmosphere of nitrogen for 14 hours
  4. additionwas added
  5. customThe mixture was degassed three times
  6. temperatureheated
  7. temperatureto reflux for 6 more hours
  8. filtrationThe mixture was filtered
  9. concentrationconcentrated
  10. customto give a crude residue

Sources & evidence

ORD record
ord-c50845bbc7ce46d9807b35da65d5b5e7
Source dataset
uspto-grants-2013_01
Patent number
US08349849B2

Reaction notes

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