M-Cresol → (S)-methyl 3-(m-tolyloxy)-2-(tritylamino)propanoate

HRID 625882Notes

Reaction equation

HRID 625882 reaction equation
[OH:1][CH2:2][C@H:3]([NH:8][C:9]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]([O:6][CH3:7])=[O:5].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:47]1[C:52](O)=[CH:51][CH:50]=[CH:49][C:48]=1[CH3:54].CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1>[C:48]1([CH3:54])[CH:49]=[CH:50][CH:51]=[C:52]([O:1][CH2:2][C@H:3]([NH:8][C:9]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:4]([O:6][CH3:7])=[O:5])[CH:47]=1

Participants

6

Reactant 4

HCID 342M-CresolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 7128367N-(Triphenylmethyl)-L-serine methyl ester

Product 1

HCID 90457174(S)-methyl 3-(m-tolyloxy)-2-(tritylamino)propanoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a round-bottom flask equipped with a stir bar was added (S)-methyl 3-hydroxy-2-(tritylamino)propanoate (10.0 g, 27.7 mmol), triphenylphosphine (7.98 g, 30.4 mmol) and toluene (100 mL). The solution was stirred at room temperature for 30 min., then to the solution was added m-cresol (3.78 mL, 36.0 mmol) and diisopropylazodicarboxylate (“DIAD”, 5.92 mL, 30.4 mmol). The solution was heated at 80° C. with stirring for 18 h. The solution was cooled to room temperature and concentrated and the resulting residue was subjected to silica gel chromatography (hexanes:EtOAc) to afford (S)-methyl 3-(m-tolyloxy)-2-(tritylamino)propanoate, 8.28 g (66%). 1H-NMR (400 MHz, CDCl3) δ 7.53 (d, J=7.6 Hz, 6H), 7.29-7.23 (m, 5H), 7.21-7.11 (m, 4H), 6.77 (d, J=7.3 Hz, 1H), 6.73-6.64 (m, 2H), 5.30 (s, 2H), 4.25 (dd, J=9.3, 4.9 Hz, 1H), 4.01 (dd, J=9.2, 6.7 Hz, 1H), 3.76-3.68 (m, 1H), 3.22 (s, 3H), 2.88 (d, J=10.5 Hz, 1H), 2.32 (s, 3H).

Workup

  1. customTo a round-bottom flask equipped with a stir bar
  2. temperatureThe solution was heated at 80° C.
  3. stirringwith stirring for 18 h
  4. temperatureThe solution was cooled to room temperature
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-114fea5981854c269fbbd56421e781e6
Source dataset
uspto-grants-2016_04
Patent number
US09308236B2

Reaction notes

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