Sodium Hydroxide → tert-Butyl ((2R,3R)-3-(benzyloxy)-1-hydroxybutan-2-yl)carbamate

HRID 1507991Notes

Reaction equation

HRID 1507991 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([O:14][C@H:15]([CH3:28])[C@H:16]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:17](O)=[O:18])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[OH-].[Na+].[O-]S([O-])(=O)=O.[Mg+2]>C(OCC)C.O>[C:24]([O:23][C:21](=[O:22])[NH:20][C@@H:16]([C@H:15]([O:14][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH3:28])[CH2:17][OH:18])([CH3:25])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 1549483L-Threonine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 21226445Aluminium lithium hydride

Product 1

HCID 11109205tert-Butyl ((2R,3R)-3-(benzyloxy)-1-hydroxybutan-2-yl)carbamateYield 71.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent2×

Procedure

To a suspension of lithium aluminum hydride (2.94 g, 78 mmol) in 50 mL diethyl ether at 0° C. was slowly added a solution of (2S,3R)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)butanoic acid (8.0 g, 25.9 mmol) in 25 mL diethyl ether. The reaction was allowed to warm to rt and stirred 1 hr. Water (3 ml) was added with caution, to the reaction mixture. This addition was followed by an addition of 15% NaOH (3 ml) and water (9 ml). These additions were made with extreme caution to control the rate of gas evolution. After stirring 1 hr at rt, MgSO4 was added and the mixture was filtered. The filtrate was concentrated to afford an oil, which was chromatographed on a 120 gm Isco cartridge using an 0-75% EtOAc/Hex gradient. The pure fractions were concentrated to afford tert-butyl((2R,3R)-3-(benzyloxy)-1-hydroxybutan-2-yl)carbamate (5.44 g, 18.42 mmol, 71.2% yield) as a colorless oil. 1H NMR (400 MHz, CCl3D) δ 7.32 (s, 5H), 5.07 (br. s., 1H), 4.64 (d, J=11.4 Hz, 1H), 4.38 (d, J=11.7 Hz, 1H), 3.83 (d, J=6.2 Hz, 1H), 3.79-3.71 (m, 1H), 3.70-3.59 (m, 2H), 2.60-2.38 (m, 1H), 1.48-1.42 (m, 9H), 1.27-1.25 (m, 3H).

Workup

  1. additionThis addition
  2. stirringAfter stirring 1 hr at rt
  3. filtrationthe mixture was filtered
  4. concentrationThe filtrate was concentrated
  5. customto afford an oil, which
  6. customwas chromatographed on a 120 gm Isco cartridge
  7. concentrationThe pure fractions were concentrated

Sources & evidence

ORD record
ord-aa8e2cc129574e0a839216d23b87544e
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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