Hydrochloric Acid → HCID 70818646, compound

HRID 331525Notes

Reaction equation

HRID 331525 reaction equation
[BH4-].[Li+].[C:3]([O:7][C:8]([NH:10][CH:11]([C:14]1[CH:24]=[CH:23][C:17]([C:18](OCC)=[O:19])=[CH:16][CH:15]=1)[CH2:12][F:13])=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl.C(=O)(O)[O-].[Na+]>O1CCCC1>[F:13][CH2:12][CH:11]([NH:10][C:8](=[O:9])[O:7][C:3]([CH3:5])([CH3:4])[CH3:6])[C:14]1[CH:15]=[CH:16][C:17]([CH2:18][OH:19])=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 70819069HCID 70819069, compound

Product 1

HCID 70818646HCID 70818646, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Lithium boranuide (208.9 mg, 9.588 mmol) was added to a stirred solution ethyl 4-[1-(tert-butoxycarbonylamino)-2-fluoro-ethyl]benzoate (1.99 g, 6.392 mmol) in tetrahydrofuran (40 mL) and the reaction warmed to 65° C. for 15 hours. The reaction mixture was cooled to ambient temperature then poured onto crushed ice whilst stirring, 1 M hydrogen chloride solution was added drop wise until no effervescence was observed. The mixture was stirred for 1 hour then saturated aqueous sodium bicarbonate solution was added until the mixture was at pH 8. The aqueous layer was extracted with ethyl acetate (×3) and the combined organic extracts dried over MgSO4, filtered and concentrated in vacuo. Purification by column chromatography (ISCO Companion, 120 g column) loaded in dichloromethane, eluted with 0 to 100% ethyl acetate/petroleum ether. Product fractions were combined and concentrated in vacuo to give tert-butyl N-[2-fluoro-1-[4-(hydroxymethyl)phenyl]ethyl]carbamate as a white solid (1.15 g, 67%). 1H NMR (400.0 MHz, DMSO-d6) δ 1.37 (s, 9H), 4.44-4.49 (m, 4H), 4.80-4.89 (m, 1H), 5.16 (t, 1H), 7.27-7.38 (m, 4H) and 7.65 (d, 1H) ppm; LC/MS m/z 214.0 [M+H]+

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. additionthen poured
  3. customonto crushed ice
  4. stirringThe mixture was stirred for 1 hour
  5. extractionThe aqueous layer was extracted with ethyl acetate (×3)
  6. dry with materialthe combined organic extracts dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography (ISCO Companion, 120 g column)
  10. washeluted with 0 to 100% ethyl acetate/petroleum ether
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6037e4aa67874fea8015693d8149e9f1
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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