Tetrabutylammonium Fluoride → Tert-butyl(1S)-1-(2-(2-hydroxyethyl)cyclopropyl)-3-methylbutylcarbamate

HRID 2065816Notes

Reaction equation

HRID 2065816 reaction equation
[Si]([O:18][CH2:19][CH2:20][CH:21]1[CH2:23][CH:22]1[C@@H:24]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:25][CH:26]([CH3:28])[CH3:27])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[OH:18][CH2:19][CH2:20][CH:21]1[CH2:23][CH:22]1[C@@H:24]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH2:25][CH:26]([CH3:28])[CH3:27]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 86638862HCID 86638862, compound

Product 1

HCID 86638863Tert-butyl(1S)-1-(2-(2-hydroxyethyl)cyclopropyl)-3-methylbutylcarbamateYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the crude TBDPS-protected alcohol 11a (464 mg, 0.742 mmol) in dry THF (6 mL) at 0° C. was added TBAF (1.0M/THF, 0.93 mL, 0.927 mmol), and the reaction mixture was allowed to warm to rt while stirring under N2. Since TLC showed incomplete reaction after 5 h, 0.75 eq. TBAF (0.56 mL) was added. After 9 h, the reaction mixture was quenched with sat. aq. NH4Cl and diluted with EtOAc. The aqueous phase was separated and extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Flash chromatography (SiO2, 5:5, hexanes/EtOAc) afforded 177 mg (88%) of the title compound as a colorless oil which solidified upon high vacuum to give a white powder. mp 49.8-50.2° C.; [α]D22 −30.8 (c 1.0, DCM); 1H NMR (300 MHz, CDCl3) δ 4.50 (appbd, 1 H, J=4.5 Hz), 3.66 (bs, 2 H), 2.94 (m, 1 H), 2.36 (bs, 1H), 1.82 (bs, 1 H), 1.71 (m, 1 H), 1.45 (s, 9 H), 1.39 (t, 2 H, J=7.2 Hz), 1.01 (bs, 2 H), 0.90 (dd, 6 H, J=10.2, 6.6 Hz), 0.50 (m, 1 H), 0.43-0.27 (m, 2 H); HRMS (ESI) m/z calcd for C15H29NO3Na 294.2045, found 294.2064.

Workup

  1. customat 0° C.
  2. customreaction after 5 h
  3. customthe reaction mixture was quenched with sat. aq. NH4Cl
  4. additiondiluted with EtOAc
  5. customThe aqueous phase was separated
  6. extractionextracted with EtOAc
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6d8b238e4469494fa342ceb73370bfeb
Source dataset
uspto-grants-2012_10
Patent number
US08288551B2

Reaction notes

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