Lithium Chloride → t-butyl (1R)-2-hydroxy-1-(4-(2-methylpentyloxy)phenyl)ethylcarbamate

HRID 1874617Notes

Reaction equation

HRID 1874617 reaction equation
[BH4-].[Na+].[Cl-].[Li+].[C:5]([O:9][C:10]([NH:12][C@H:13]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([CH3:30])[CH2:27][CH2:28][CH3:29])=[CH:20][CH:19]=1)[C:14](OC)=[O:15])=[O:11])([CH3:8])([CH3:7])[CH3:6]>C(O)C.O1CCCC1>[OH:15][CH2:14][C@H:13]([NH:12][C:10](=[O:11])[O:9][C:5]([CH3:6])([CH3:8])[CH3:7])[C:18]1[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH:26]([CH3:30])[CH2:27][CH2:28][CH3:29])=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 4311764Sodium borohydrideHCID 67085932(2R)-methyl 2-(tert-butoxycarbonylamino)-2-(4-(2-methylpentyloxy)phenyl)acetate

Product 1

HCID 67433195t-butyl (1R)-2-hydroxy-1-(4-(2-methylpentyloxy)phenyl)ethylcarbamateYield 92%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium borohydride (1.346 g, 35.6 mmol) in ethanol (50 mL) at 0° C. was added lithium chloride (1.508 g, 35.6 mmol). The mixture was stirred at 0° C. for 10 min. A solution of (2R)-methyl 2-(tert-butoxycarbonylamino)-2-(4-(2-methylpentyloxy)phenyl)acetate (5.00 g, 13.68 mmol) in tetrahydrofuran (50.0 mL) was then added via cannula. The reaction mixture was warmed up to room temperature and was stirred at room temperature for 3 h. The reaction mixture was cooled to 0° C. and was quenched by the slow addition of saturated aqueous NH4Cl solution (30 mL). The reaction mixture was transferred to a separatory funnel containing water (50 mL). The aqueous layer was extracted with ethyl acetate (3×150 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (30%→45% ethyl acetate in hexanes) to afford t-butyl (1R)-2-hydroxy-1-(4-(2-methylpentyloxy)phenyl)ethylcarbamate (4.24 g, 92% yield) as a colorless solid: 1H NMR (400 MHz, DMSO-d6) δ 7.17 (d, J=8.6 Hz, 2H), 7.12 (d, J=8.3 Hz, 1H), 6.84 (d, J=8.6 Hz, 2H), 4.72 (t, J=5.8 Hz, 1H), 4.44 (q, J=6.8 Hz, 1H), 3.79 (dd, J=9.3, 5.8 Hz, 1H), 3.70 (dd, J=9.3, 6.5 Hz, 1H), 3.37-3.49 (m, 2H), 1.80-1.92 (m, 1H), 1.36 (s, 9H), 1.23-1.47 (m, 3H), 1.13-1.21 (m, 1 H), 0.95 (d, J=6.5 Hz, 3H), 0.88 (t, J=7.1 Hz, 3H); LRMS (ESI) m/e 338.2 [(M+H)+, calcd for C19H32NO4 338.2].

Workup

  1. temperatureThe reaction mixture was warmed up to room temperature
  2. stirringwas stirred at room temperature for 3 h
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. customwas quenched by the slow addition of saturated aqueous NH4Cl solution (30 mL)
  5. customThe reaction mixture was transferred to a separatory funnel
  6. additioncontaining water (50 mL)
  7. extractionThe aqueous layer was extracted with ethyl acetate (3×150 mL)
  8. washThe combined organic layers were washed with brine (50 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography on silica gel (30%→45% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b53152c70fa84aaebd791e98c7eb6a75
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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