Tetrahydrofuran → HCID 68294279, compound

HRID 2279581Notes

Reaction equation

HRID 2279581 reaction equation
[Si:1]([O:8][CH2:9][CH:10]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=1)[CH2:11][CH:12]=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CC(=CC)C.C1C[O:30]CC1.[O-]Cl=O.[Na+]>C(O)(C)(C)C.O>[Si:1]([O:8][CH2:9][CH:10]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=1)[CH2:11][C:12]([OH:30])=[O:13])([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 86705564HCID 86705564, compound

Product 1

HCID 68294279HCID 68294279, compoundYield 85.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

To a solution of 314 (302 mg, 0.913 mmol) in tert-BuOH (20 mL) and H2O (5 mL) was added 2M solution of 2-methyl-2-butene in THF (4.56 mL, 9.13 mmol) then NaH2PO4 (1.204 g, 10.0 mmol). The reaction was stirred 5 min, then NaClO2 (495 mg, 5.48 mmol) was added and the reaction stirred at RT overnight. The reaction was partitioned between EtOAc (50 mL) and 0.5M HCl (30 mL), phases separated and the aqueous phase extracted with EtOAc (50 mL). The combined organic extracts were washed with satd. aq. NaCl (50 mL), dried (MgSO4), filtered and concentrated. The crude product was purified by SiO2 chromatography eluting with 10% EtOAc/hexane to afford 270 mg (85%) of 4-(tert-butyldimethylsilyloxy)-3-(3-chloro-4-fluorophenyl)butanoic acid (316) as a gray crystalline solid: 1H NMR (400 MHz, CDCl3) δ 7.27 (dd, J=2.3, 7.1 Hz, 1H), 7.08 (m, 2H), 3.74 (m, 1H), 3.61 (m, 1H), 3.26 (m, 1H), 2.91 (m, 1H), 2.61 (m, 1H), 0.86 (s, 9H), −0.03 (d, J=1.6 Hz, 6H); MS LRMS (APCI neg) m/e=345.1 (M−H).

Workup

  1. stirringthe reaction stirred at RT overnight
  2. customThe reaction was partitioned between EtOAc (50 mL) and 0.5M HCl (30 mL), phases
  3. customseparated
  4. extractionthe aqueous phase extracted with EtOAc (50 mL)
  5. washThe combined organic extracts were washed with satd
  6. dry with materialaq. NaCl (50 mL), dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by SiO2 chromatography
  10. washeluting with 10% EtOAc/hexane

Sources & evidence

ORD record
ord-997e59cfb6124ecb8f1ad5303acd1701
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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