Water → (2S,3S)-2-[Cbz(methyl)amino]-3-methylpentan-1-ol

HRID 74715Notes

Reaction equation

HRID 74715 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH3:20])[C@H:12]([C:17](O)=[O:18])[C@H:13]([CH2:15][CH3:16])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.O1CCCC1.O>O1CCCC1.C(=O)([O-])[O-].[Na+].[Na+].COC(C)(C)C>[CH2:1]([O:8][C:9](=[O:10])[N:11]([C@@H:12]([C@@H:13]([CH3:14])[CH2:15][CH3:16])[CH2:17][OH:18])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 962WaterHCID 2723981Borane;tetrahydrofuranHCID 7019518N-[(Benzyloxy)carbonyl]-N-methyl-L-isoleucine

Product 1

HCID 11777636(2S,3S)-2-[Cbz(methyl)amino]-3-methylpentan-1-olYield 97.4%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 10340Sodium CarbonateSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of N-[(benzyloxy)carbonyl]-N-methyl-L-isoleucine (52.37 g, 187.5 mmol, 1 eq.) in tetrahydrofuran (524 mL, 0.35 M) was added borane-tetrahydrofuran complex (1 M in tetrahydrofuran, 375 mL, 375 mmol, 2 eq.) slowly over 1 hour and the reaction was allowed to stir for 18 hours at room temperature. The reaction was cooled to 0° C. and water (30 mL) was added over 30 minutes. The reaction mixture was diluted with 1 M aqueous sodium carbonate solution (100 mL) and tert-butyl methyl ether (250 mL). The aqueous layer was back-extracted with tert-butyl methyl ether (100 mL). The combined organic layers were washed with 1 M aqueous sodium carbonate solution (100 mL), washed with brine (200 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to provide #1 (48.44 g, 97% yield) as a pale yellow oil, which was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers: δ 7.26-7.41 (m, 5H), [5.06 (AB quartet, JAB=12.9 Hz, ΔνAB=22.8 Hz) and 5.06 (AB quartet, JAB=9.0 Hz, ΔνAB=9.0 Hz), total 2H], [4.65 (t, J=5.3 Hz) and 4.59 (t, J=5.4 Hz), total 1H], 3.67-3.80 (m, 1H), 3.51-3.60 (m, 1H), 3.41-3.51 (m, 1H), 2.75 and 2.71 (2 s, total 3H), 1.49-1.64 (br m, 1H), 1.24-1.37 (br m, 1H), 0.90-1.02 (br m, 1H), 0.74-0.87 (m, 6H).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. extractionThe aqueous layer was back-extracted with tert-butyl methyl ether (100 mL)
  3. washThe combined organic layers were washed with 1 M aqueous sodium carbonate solution (100 mL)
  4. washwashed with brine (200 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-71b2251ea77f4b8f859563639b942cf2
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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