Tetrahydrofuran → HCID 67413236, compound

HRID 1036432Notes

Reaction equation

HRID 1036432 reaction equation
[C:1]([O:5][C:6](=[O:38])[NH:7][C@@:8]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:26][CH:27]3[CH2:32][CH2:31][CH:30]([CH:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)[CH2:29][CH2:28]3)[C:18]=2[C:22]([F:25])([F:24])[F:23])[CH:13]=1)([CH3:11])[CH2:9][OH:10])([CH3:4])([CH3:3])[CH3:2].N1C=NN=N1.[O:44]1CCCC1.C(N(CC)[P:52]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:38])[NH:7][C@@:8]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:26][CH:27]3[CH2:28][CH2:29][CH:30]([CH:33]4[CH2:34][CH2:35][CH2:36][CH2:37]4)[CH2:31][CH2:32]3)[C:18]=2[C:22]([F:24])([F:25])[F:23])[CH:13]=1)([CH3:11])[CH2:9][O:10][P:52]([O:53][C:54]([CH3:55])([CH3:56])[CH3:57])([O:58][C:59]([CH3:60])([CH3:61])[CH3:62])=[O:44])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 4251849Di-tert-butyl diethylphosphoramiditeHCID 67414344HCID 67414344, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 67413236HCID 67413236, compoundYield 82.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {(R)-1-[6-(4-Cyclopentyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-2-hydroxy-1-methyl-ethyl}-carbamic acid tert-butyl ester (11 mg, 0.000020 mol) and 1H-tetrazole (14 mg, 0.00020 mol) in tetrahydrofuran (3 mL, 0.04 mol) was added di-tert-butyl N,N-Diethylphosphoramidite (28 μL, 0.00010 mol) at RT. The reaction was then quenched with 10% NaS2O3 in saturated sodium bicarbonate, extracted with EtOAc, washed with saturated sodium chloride and then dried with Na2SO4. The drying agent was filtered and the organic layer was concentrated under vacuum, yielding the crude product. The crude was taken up in DCM and purified using silica gel chromatography (24 g column), 0-100% ethyl acetate in hexanes) to give 12 mg of the desired compound as a white solid (77%). ESI-MS: 728 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ=8.18-8.08 (m, 1H), 7.92 (d, J=9.0 Hz, 1H), 7.63-7.42 (m, 2H), 7.22 (dd, J=5.0, 9.0 Hz, 1H), 4.32-4.11 (m, 1H), 3.98-3.80 (m, 2H), 2.18-1.98 (m, 2H), 1.92-0.71 (m, 46H)

Workup

  1. customThe reaction was then quenched with 10% NaS2O3 in saturated sodium bicarbonate
  2. extractionextracted with EtOAc
  3. washwashed with saturated sodium chloride
  4. dry with materialdried with Na2SO4
  5. filtrationThe drying agent was filtered
  6. concentrationthe organic layer was concentrated under vacuum
  7. customyielding the crude product
  8. custompurified

Sources & evidence

ORD record
ord-ec36adc6874b449bbe0ee7ffc7184a9f
Source dataset
uspto-grants-2013_10
Patent number
US08546359B2

Reaction notes

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