(2S)-Cyclopropyl{[(1S)-1-phenylethyl]amino}acetic acid → HCID 44596483, compound

HRID 386490Notes

Reaction equation

HRID 386490 reaction equation
[CH:1]1([C@H:4]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:10])[C:5](O)=[O:6])[CH2:3][CH2:2]1.CSC.B>C1COCC1>[CH:1]1([C@H:4]([NH:8][C@H:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH3:10])[CH2:5][OH:6])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 11148702(2S)-Cyclopropyl{[(1S)-1-phenylethyl]amino}acetic acidHCID 12423031(Dimethyl sulfide)trihydroboron

Product 1

HCID 44596483HCID 44596483, compoundYield 44.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-2-cyclopropyl-2-[(S)-1-phenylethylamino]acetic acid (400 g, 1.82 mol) in dry THF (5.2 L) at 0° C. was added borane dimethylsulfide (neat) (485 g, 6.39 mol) with vigorous stirring. The reaction mixture was stirred overnight at room temperature. Reaction progress was monitored by HPLC. Stirring was continued until the acid was consumed completely (18-20 h). Upon completion the reaction mixture was cooled to 0° C. and methanol (6 L) was added dropwise. The mixture was concentrated under vacuum and the residue was dissolved in chloroform (5 L). The organic layer was washed with 10% aqueous NaHCO3 solution (2×1 L) followed by brine, dried over Na2SO4, filtered and concentrated to afford a tan-yellow oil. The oil was distilled under reduced pressure to afford (S)-2-cyclopropyl-2-[(S)-1-phenylethylamino]ethanol (166 g, 44% yield) as a colorless oil: by 175-184° C., 0.1 mm Hg; [α]25D −52.1 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1H NMR (400 MHz, CDCl3) δ 7.33-7.20 (m, 5H), 3.91-3.86 (m, 1H), 3.67 (dd, JAB=10.6, JAX=3.8 Hz, 1H), 3.39 (dd, JBA=10.6, JBX=4.3 Hz, 1H), 2.40 (s br, 2H), 1.70-1.65 (m, 1H), 1.35 (d, J=6.6 Hz, 3H), 0.88-0.82 (m, 1H), 0.47-0.37 (m, 2H), 0.05-−0.06 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ 146.8, 127.6, 126.2, 125.9, 63.0, 60.5, 54.4, 24.4, 13.3, 3.0, 1.5; LRMS (ESI) m/e 206.3 [(M+H)+, calcd for C13H20NO 206.2].

Workup

  1. customReaction progress
  2. stirringStirring
  3. customwas consumed completely (18-20 h)
  4. temperatureUpon completion the reaction mixture was cooled to 0° C.
  5. additionmethanol (6 L) was added dropwise
  6. concentrationThe mixture was concentrated under vacuum
  7. dissolutionthe residue was dissolved in chloroform (5 L)
  8. washThe organic layer was washed with 10% aqueous NaHCO3 solution (2×1 L)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a tan-yellow oil
  13. distillationThe oil was distilled under reduced pressure

Sources & evidence

ORD record
ord-724d8622543c4ffdbb549fbb1d1315d5
Source dataset
uspto-grants-2013_02
Patent number
US08372847B2

Reaction notes

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