(Diethylamino)sulfur trifluoride → Benzyl 4-fluoro-4-methyltetrahydrofuran-3-ylcarbamate

HRID 877673Notes

Reaction equation

HRID 877673 reaction equation
C(N(S(F)(F)[F:7])CC)C.O[C:11]1([CH3:27])[CH2:15][O:14][CH2:13][CH:12]1[NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>ClCCl>[F:7][C:11]1([CH3:27])[CH2:15][O:14][CH2:13][CH:12]1[NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 68291164Benzyl 4-hydroxy-4-methyltetrahydrofuran-3-ylcarbamate

Product 1

HCID 68291260Benzyl 4-fluoro-4-methyltetrahydrofuran-3-ylcarbamateYield 29.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(Diethylamino)sulphur trifluoride (2.103 mL, 15.92 mmol) was added dropwise to a solution of impure benzyl 4-hydroxy-4-methyltetrahydrofuran-3-ylcarbamate (2.00 g, from Step 4) in dichloromethane (50 mL) at −78° C. After 45 min at −78° C., the mixture was quenched with saturated sodium bicarbonate (100 mL) and allowed to warm to room temperature. After separation of the two phases, the aqueous phase was extracted with dichloromethane (3×50 mL). The combined extracts were dried (MgSO4) and concentrated. The mixture was purified by silica gel chromatography, eluting with 10-50% ethyl acetate in hexanes. None of the fractions were found to be free of impurities. All fractions containing the desired product were combined to give impure benzyl 4-fluoro-4-methyltetrahydrofuran-3-ylcarbamate (597 mg). The mixture was taken to the next step without purification.

Workup

  1. customthe mixture was quenched with saturated sodium bicarbonate (100 mL)
  2. customAfter separation of the two phases
  3. extractionthe aqueous phase was extracted with dichloromethane (3×50 mL)
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. concentrationconcentrated
  6. customThe mixture was purified by silica gel chromatography
  7. washeluting with 10-50% ethyl acetate in hexanes
  8. additionAll fractions containing the desired product

Sources & evidence

ORD record
ord-fcde01112f1c4b6f96f3f4a7f9d2c0f9
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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