Triphenylphosphine → (2R)-Methyl 2-(tert-butoxycarbonylamino)-(4-((S)-2-methyl-butoxy)-phenyl)acetate

HRID 454996

Reaction equation

HRID 454996 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21][C@@H:22]([CH2:25][CH3:26])[CH2:23]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C@@H:22]([CH3:23])[CH2:25][CH3:26])=[CH:16][CH:15]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 2723602(S)-2-methyl-1-butanolHCID 5363146Diisopropyl azodicarboxylateHCID 10934864Methyl (2R)-2-{[(tert-butoxy)carbonyl]amino}-2-(4-hydroxyphenyl)acetate

Product 1

HCID 67438449(2R)-Methyl 2-(tert-butoxycarbonylamino)-(4-((S)-2-methyl-butoxy)-phenyl)acetateYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 0° C. solution of (R)-Methyl 2-(tert-butoxycarbonylamino)-2-(4-hydroxyphenyl)acetate (2.8 g, 10 mmol), (S)-2-methyl-1-butanol (1.1 mL, 10 mmol), triphenylphosphine (2.6 g, 10 mmol), and tetrahydrofuran (100 mL) was treated dropwise with diisopropylazodicarboxylate (1.9 mL, 10 mmol) via syringe. The resulting reaction mixture was allowed to warm to room temperature and maintained overnight. The reaction was concentrated and the residue was purified by column chromatography on silica gel (5%-10% ethyl acetate in hexanes) to afford (2R)-Methyl 2-(tert-butoxycarbonylamino)-(4-((S)-2-methyl-butoxy)-phenyl)acetate (2.8 g, 80% yield) as a clear, colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J=7.3 Hz, 2H), 6.88 (d, J=8.6 Hz, 2H), 5.49 (d, J=6.6 Hz, 1H), 5.26 (d, J=7.3 Hz, 1H), 3.81 (dd, J=9.1, 6.1 Hz, 1H), 3.73 (s, 3H), 3.69-3.76 (m, 1H), 1.86 (dq, J=13.1, 6.5 Hz, 1H), 1.52-1.61 (m, 1H), 1.45 (s, 9H), 1.22-1.33 (m, 2H), 1.02 (d, J=6.8 Hz, 3H), 0.95 (t, J=7.5 Hz, 3H); LRMS (ESI) m/e 352.2 [(M+H)+, calcd for C19H30NO5 352.5].

Workup

  1. customThe resulting reaction mixture
  2. temperaturemaintained overnight
  3. concentrationThe reaction was concentrated
  4. customthe residue was purified by column chromatography on silica gel (5%-10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f8b0fafec7b14b4392a99764911949bc
Source dataset
uspto-grants-2013_07
Patent number
US08497271B2

Linked notes

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