Ammonium Chloride → (3S)-tert-butyl 3-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

TBAF (7.27 mL of 1.0 M in THF, 7.27 mmol) was added dropwise over 5 min to a THF (30 mL) solution of (3S)-tert-butyl 3-((tert-butyldiphenylsilyloxy)methyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (mixture of cis/trans isomers) (3.13 g, 6.93 mmol) and the mixture was stirred at ambient temperature for 4.75 h. After the addition of saturated NH4Cl solution (5 mL), most of the volatile material was removed in vacuo and the residue partitioned between CH2Cl2 (70 mL) and 50% saturated NH4Cl solution (30 mL). The aqueous phase was extracted with CH2Cl2 (30 mL) and the combined organic phase was dried (MgSO4), filtered, concentrated in vacuo and then exposed to high vacuum overnight. The crude material was purified using a flash chromatography (silica gel; 40-50% EtOAc/hexanes) to afford (3S)-tert-butyl 3-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (1.39 g, 94% yield) as a mixture of cis/trans isomers and a colorless oil. [Note: the exact cis/trans isomer ratio was not determined at this stage.] LC/MS (M+Na)+=236.20. 1H NMR (400 MHz, DMSO-d6, δ=2.5 ppm) δ ppm 4.70 (t, J=5.7, 1H), 3.62-3.56 (m, 1H), 3.49-3.44 (m, 1H), 3.33-3.27 (m, 1H), 3.08-3.04 (m, 1H), 2.07 (br m, 1H), 1.93-1.87 (m, 1H), 1.51-1.44 (m, 1H), 1.40 (s, 9H), 0.76-0.71 (m, 1H), 0.26 (m, 1H).

1. custommost of the volatile material was removed in vacuo
2. customthe residue partitioned between CH2Cl2 (70 mL) and 50% saturated NH4Cl solution (30 mL)
3. extractionThe aqueous phase was extracted with CH2Cl2 (30 mL)
4. dry with materialthe combined organic phase was dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customexposed to high vacuum overnight
8. customThe crude material was purified

ORD record

ord-423b93ebc26448f8a7541ab3a2cf255e

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006455B2