Sodium Hydroxide → tert-Butyl ((2S)-1-hydroxy-3-((tetrahydro-2H-pyran-2-yl)oxy)propan-2-yl)carbamate

HRID 524357Notes

Reaction equation

HRID 524357 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][O:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][O:17]1)[C:10](OC)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Li+].COC1C=CC(C=O)=CC=1.[OH-].[Na+]>C(OCC)C.C(OCC)(=O)C>[OH:11][CH2:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:14][O:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][O:17]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 312444-MethoxybenzaldehydeHCID 4148881Lithium borohydrideHCID 13969838(2R)-Methyl 2-((tert-butoxycarbonyl)amino)-3-((tetrahydro-2H-pyran-2-yl)oxy)propanoate

Product 1

HCID 13969840tert-Butyl ((2S)-1-hydroxy-3-((tetrahydro-2H-pyran-2-yl)oxy)propan-2-yl)carbamate

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a 3 L three neck flask fitted with a thermometer, magnetic stirrer, under argon was added 2 (128 g, 0.42 mol) in diethyl ether (1.5 L). A clear yellow solution formed after one hour of stirring at room temperature. The solution was cooled to 10° C. with an ice/water bath. Lithium borohydride (9.3 g, 0.42 mol) was added in three portions over 30 minutes to keep the temperature below 18° C. The reaction mixture was warmed to 32° C. and was complete after 60 min by TLC (EtOAc:Hexanes; 3:7, anisaldehyde dip reagent). The reaction mixture was transferred to a 4 L flask and stirred vigorously while 1M NaOH (350 mL) was added slowly to pH 11 and stirred an additional 30 min. Ethyl acetate (500 mL) was added to the mixture and stirred 5 min. The layers were separated. The organic layer was washed with brine (1×600 mL) and dried over granular Na2SO4 (100 g) for 15 min. The mixture was filtered and concentrated under reduced pressure overnight to 109 g (94%) of product 3 as a waxy white crystalline solid. 1H NMR (60 MHz, CDCl3) δ 5.0-5.3 (br m, 1H), 3.2-4.6 (m, 8H), 2.4-3.0 (m, 1H), 1.3-1.7 (m, 15H).

Workup

  1. customA clear yellow solution formed after one hour
  2. temperatureThe solution was cooled to 10° C. with an ice/water bath
  3. customthe temperature below 18° C
  4. temperatureThe reaction mixture was warmed to 32° C.
  5. customThe reaction mixture was transferred to a 4 L flask
  6. additionwas added slowly to pH 11
  7. stirringstirred an additional 30 min
  8. stirringstirred 5 min
  9. customThe layers were separated
  10. washThe organic layer was washed with brine (1×600 mL)
  11. dry with materialdried over granular Na2SO4 (100 g) for 15 min
  12. filtrationThe mixture was filtered
  13. concentrationconcentrated under reduced pressure overnight to 109 g (94%) of product 3 as a waxy white crystalline solid

Sources & evidence

ORD record
ord-cbfcf456cba2490dbf03e1accee36709
Source dataset
uspto-grants-2016_05
Patent number
US09340534B2

Reaction notes

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