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

HRID 41103

반응식

HRID 41103 반응식
[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

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 1362874-Fluoro-3-nitrotolueneHCID 1515269(R)-2-Aminomethyl-4-Boc-morpholine

생성물 1

HCID 67170278(R)-tert-butyl 2-((2-amino-4-methylphenylamino)methyl)morpholine-4-carboxylate수율 99.6%

시약·촉매·용매 2

HCID 23994Zinc촉매HCID 887Methanol용매

반응 조건

온도
140 °C

실험 절차

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.

후처리

  1. temperaturecooled to room temperature

출처 및 근거

ORD 기록
ord-48826e0ef53c44c2b9ad5f3907d5d719
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530467B2

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