Hydrochloric Acid → tert-butyl N-((1R,3S)-3-(hydroxymethyl)cyclopentyl)carbamate

HRID 45254Notes

Reaction equation

HRID 45254 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][C@H:11]([C:14](O)=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.ClC(OCC(C)C)=O.[BH4-].[Na+].Cl>C1COCC1.C1COCC1.O>[OH:15][CH2:14][C@H:11]1[CH2:12][CH2:13][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:10]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 1512529(1S,3R)-3-(((tert-butoxy)carbonyl)amino)cyclopentane-1-carboxylic acidHCID 4311764Sodium borohydride

Product 1

HCID 11962831tert-butyl N-((1R,3S)-3-(hydroxymethyl)cyclopentyl)carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
-20 °C

Procedure

To a solution of 2 g (8.7 mmol) of (1S,3R)-3-[(tert-butoxycarbonyl)amino]cyclopentanecarboxylic acid and 1.33 mL (9.6 mmol) of Et3N in 20 mL of anhydrous THF are added dropwise, at −20° C., 1.2 mL (9.2 mmol) of isobutyl chloroformate. The medium is stirred for 45 minutes at −20° C. and the insoluble material formed is then filtered off. A solution of 1 g (26.2 mmol) of sodium borohydride in a THF/H2O mixture (16 mL/4 mL) is added dropwise to the filtrate at −10° C. and stirring is then continued, while allowing the temperature to return to room temperature. 100 mL of 0.1N HCl are then added slowly and the reaction medium is then extracted with 2×200 mL of EtOAc, dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by chromatography on a column of silica gel, eluting with a DCM/MeOH mixture (95/5), 1.4 g of tert-butyl [(1R,3S)-3-(hydroxymethyl)cyclopentyl]carbamate are obtained in the form of an oil.

Workup

  1. customthe insoluble material formed
  2. filtrationis then filtered off
  3. stirringstirring
  4. customto return to room temperature
  5. extractionthe reaction medium is then extracted with 2×200 mL of EtOAc
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customAfter purification by chromatography on a column of silica gel
  10. washeluting with a DCM/MeOH mixture (95/5), 1.4 g of tert-butyl [(1R,3S)-3-(hydroxymethyl)cyclopentyl]carbamate
  11. customare obtained in the form of an oil

Sources & evidence

ORD record
ord-616dc058681947999072c875d140c6eb
Source dataset
uspto-grants-2013_09
Patent number
US08541455B2

Reaction notes

Loading…