Sodium borohydride → (3S)-3-Benzyloxycarbonylamino-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester

HRID 1432362Notes

Reaction equation

HRID 1432362 reaction equation
[BH4-].[Na+].[C:3]([O:7][C:8](=[O:36])[CH2:9][CH:10]([NH:25][C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])[C:11](=[O:24])[CH2:12][O:13][C:14]1[C:19]([F:20])=[C:18]([F:21])[CH:17]=[C:16]([F:22])[C:15]=1[F:23])([CH3:6])([CH3:5])[CH3:4]>C1COCC1>[C:3]([O:7][C:8](=[O:36])[CH2:9][C@H:10]([NH:25][C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])[CH:11]([OH:24])[CH2:12][O:13][C:14]1[C:19]([F:20])=[C:18]([F:21])[CH:17]=[C:16]([F:22])[C:15]=1[F:23])([CH3:6])([CH3:4])[CH3:5]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 865944013-Benzyloxycarbonylamino-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester

Product 1

HCID 57725378(3S)-3-Benzyloxycarbonylamino-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaBH4 (1.65 g) was added portionwise to a stirred solution of 3-benzyloxycarbonylamino-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester (21.1 g) in anhydrous THF (220 mL) at −20° C. under nitrogen. After stirring at this temperature for 3 hours, the reaction was quenched by the addition of saturated ammonium chloride solution and diluted with DCM. The organic layer was removed and the aqueous layer re-extracted with DCM. The combined organic extracts were washed with brine, dried (magnesium sulfate) and concentrated. The residue was purified by column chromatography (10%-20% ethyl acetate/hexane). The sub-title compound as a white solid (14.6 g, 73%); 1H NMR (400 MHz, CDCl3) δ 1.45 (9H, s), 2.61-2.77 (2H, m), 3.16-3.36 (1H, 2×brd d), 4.12-4.22 (2H, m), 4.30-4.33 (1H, m), 5.44-5.69 (1H, 2×d), 6.78-6.86 (1H, m), 7.35-7.36 (5H, m); 19F NMR (346 MHz, CDCl3) (proton decoupled) δ −139.87, −139.89, −139.93, −139.95, −139.98, −157.02, −157.05, −157.06, −157.08, −157.09, −157.10, −157.12; ES (+) 488.27 (M+H).

Workup

  1. customthe reaction was quenched by the addition of saturated ammonium chloride solution
  2. additiondiluted with DCM
  3. customThe organic layer was removed
  4. extractionthe aqueous layer re-extracted with DCM
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (10%-20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-56f915bfc67c49d68cbf3ddfa2b78f11
Source dataset
uspto-grants-2009_11
Patent number
US07612091B2

Reaction notes

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