Acetic Acid → (R)-tert-butyl 2-((2-amino-4-methylphenylamino)methyl)morpholine-4-carboxylate

HRID 41103

Reaction equation

[NH2:1][CH2:2][C@H:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.CCN(C(C)C)C(C)C.F[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=1[N+:33]([O-])=O.C(O)(=O)C>CO.[Zn]>[NH2:33][C:27]1[CH:28]=[C:29]([CH3:32])[CH:30]=[CH:31][C:26]=1[NH:1][CH2:2][C@H:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of (R)-tert-butyl 2-(aminomethyl)morpholine-4-carboxylate (0.715 g, 3.31 mmol), DIPEA (0.577 mL, 3.31 mmol), and 1-fluoro-4-methyl-2-nitrobenzene (0.513 g, 3.31 mmol) in MeOH (14 mL) was heated at 140° C. in A microwave reactor for 30 min and then cooled to room temperature. Acetic acid (1.9 mL, 33.1 mmol) was added, followed by zinc (2.162 g, 33.1 mmol). The resulting mixture was stirred at room temperature for 90 min to afford the (R)-tert-butyl 2-((2-amino-4-methylphenylamino)methyl)morpholine-4-carboxylate product (1.06 g), which was used without further purification in the next step. The product was analyzed on analytical HPLC MS using the high pH gradient method (mobile phase: 5-95% B; A: H2O with 10 mM NH4CO3 and 0.375% NH4OH v/v; B: CH3CN; 2.25 min run; X-Bridge C18; column size: 2.1×30 mm; and particle size: 5 μm). MS m/z 322.4 [M+H]+ (ESI), Rt 1.80 min.

Workup

temperaturecooled to room temperature

Sources & evidence

ORD record: ord-48826e0ef53c44c2b9ad5f3907d5d719
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530467B2

Linked notes

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