Methyl chloroformate → methyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate

HRID 1063271Notes

Reaction equation

HRID 1063271 reaction equation
[CH2:1]([O:3][C@H:4]1[CH2:8][NH:7][CH2:6][C@H:5]1[NH:9][C:10]1[C:15]([CH2:16][CH3:17])=[N:14][CH:13]=[C:12]([CH2:18][CH3:19])[N:11]=1)[CH3:2].C(N(CC)CC)C.Cl[C:28]([O:30][CH3:31])=[O:29].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:16]([C:15]1[C:10]([NH:9][C@H:5]2[C@@H:4]([O:3][CH2:1][CH3:2])[CH2:8][N:7]([C:28]([O:30][CH3:31])=[O:29])[CH2:6]2)=[N:11][C:12]([CH2:18][CH3:19])=[CH:13][N:14]=1)[CH3:17]

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 69689234N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine

Product 1

HCID 86591414methyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylateYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine (4.50 g, 17 mmole) in CH2Cl2 (0.1 M, 170 mL) under N2 at 0° C. was added triethyl amine (7.09 mL, 3.0 eq.). Methyl chloroformate (1.44 mL, 1.1 eq.) was added drop-wise over 15 min. After 1 hour, the reaction mixture was poured into saturated aqueous NaHCO3 (150 mL). The aqueous layer was extracted with CH2Cl2 (1×200 ml), dried with MgSO4, filtered and concentrated. Purification with Biotage MPLC (40 g, 10-50% ethyl acetate in heptane gradient) provided 5.35g (98%) of methyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate as an oil. IR (liq.) 2972, 2937, 2877, 2338, 1937, 1708, 1581, 1546, 1499, 1453, 1392, 1189, 1174, 1135, 1103 (s) cm−1 HRMS (ESI) calcd for C16H26N4O3+H1 323.2083. found 323.2089. Anal. Calcd for C16 H26 N4O3: C, 59.61; H, 8.13; N, 17.38. Found: C, 59.23; H, 8.35; N, 17.33.

Workup

  1. extractionThe aqueous layer was extracted with CH2Cl2 (1×200 ml)
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification with Biotage MPLC (40 g, 10-50% ethyl acetate in heptane gradient)

Sources & evidence

ORD record
ord-a01a856acb514643a2bf2e5da712fc82
Source dataset
uspto-grants-2005_11
Patent number
US06964965B2

Reaction notes

Loading…