Hydrochloric Acid → N-Boc-trans-4-hydroxy-L-prolinol

HRID 1946605Notes

Reaction equation

HRID 1946605 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14](OC)=[O:15])[CH2:3]1.[Li+].[BH4-].O.Cl>C1COCC1>[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([CH2:14][OH:15])[CH2:3]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 4148881Lithium borohydride

Product 1

HCID 11275979N-Boc-trans-4-hydroxy-L-prolinolYield 95.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of compound 236 (6.4 g, 26.09 mmol) in THF (80 mL) at 0° C. was added a solution of LiBH4 (2.063 g, 94.76 mmol) in one shot. The suspension was stirred at 0° C. for 1 h then at room temperature overnight. The mixture was cooled to 0° C. and water (52 mL) then 6N HCl (20 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×70 mL). The combined organics were washed with 2N NaOH, 2N HCl and brine (20 mL each). The organic layers were dried over Na2SO4 filtered and concentrated to afford title compound 237 (5.4 g, 95%) as clear oil. LRMS (ESI): (calc.) 217.13 (found) 256.3 (M+K).

Workup

  1. customat room temperature
  2. customovernight
  3. temperatureThe mixture was cooled to 0° C.
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×70 mL)
  6. washThe combined organics were washed with 2N NaOH, 2N HCl and brine (20 mL each)
  7. dry with materialThe organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-8328d7c2a5a64cf79d5d7f1b2f1b4f62
Source dataset
uspto-grants-2013_03
Patent number
US08399452B2

Reaction notes

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