Ammonium Chloride → (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)-4-(5-fluoro-2-methoxyphenyl)-4-hydroxybutylcarbamate

HRID 1426894Notes

Reaction equation

HRID 1426894 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:11](=[O:21])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:22][C:23]1[CH:24]=[CH:25][C:26]([O:31][CH3:32])=[C:27]([Mg]Br)[CH:28]=1.[BH4-].[Na+].[NH4+].[Cl-]>C1COCC1.CO>[Si:1]([O:8][C@H:9]([CH2:10][CH:11]([C:25]1[CH:24]=[C:23]([F:22])[CH:28]=[CH:27][C:26]=1[O:31][CH3:32])[OH:21])[CH2:13][NH:12][C:14](=[O:15])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 11220792(R)-1-Boc-4-[(tert-butyldimethylsilyl)oxy]pyrrolidin-2-oneHCID 178491810HCID 178491810, compound

Product 1

HCID 67470707(R)-tert-butyl 2-(tert-butyldimethylsilyloxy)-4-(5-fluoro-2-methoxyphenyl)-4-hydroxybutylcarbamateYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-oxopyrrolidine-1-carboxylate (6.00 g, 19.0 mmol) in THF (36 mL) at 0° C. was added a 0.5 M solution of (5-fluoro-2-methoxyphenyl)magnesium bromide in THF (50.0 mL, 25.0 mmol). The resulting mixture was stirred at 0° C. for 30 minutes, then treated with MeOH (60 mL) and NaBH4 (0.966 g, 25.2 mmol). After stirring at 0° C. for an additional 30 minutes, the reaction mixture was poured into saturated aqueous NH4Cl (40 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material which was purified by silica column chromatography, eluting with 0-2% MeOH/DCM to afford (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)-4-(5-fluoro-2-methoxyphenyl)-4-hydroxybutylcarbamate (which was assumed to be a mixture of the syn and anti isomers), (4.81 g, 57.0% yield). 1H NMR (CDCl3) δ 7.20 (m, 1H), 6.90 (m, 1H), 6.77 (m, 1H), 5.12 (m, 1H), 4.10 (m, 1H), 3.82 (m, 3H), 3.29 (m, 2H), 1.71-1.93 (m, 2H), 1.45 (s, 9H), 0.93 (d, 9H), 0.11-0.14 (m, 6H).

Workup

  1. stirringAfter stirring at 0° C. for an additional 30 minutes
  2. extractionextracted with EtOAc (2×50 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude material which
  8. customwas purified by silica column chromatography
  9. washeluting with 0-2% MeOH/DCM

Sources & evidence

ORD record
ord-a7681bb770df4267815091bb557307cc
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

Loading…