Water → (R)-tert-butyl 2-((S)-(3-chlorophenyl)(2-(methoxycarbonylamino)ethoxy)methyl)morpholine-4-carboxylate

HRID 253591Notes

Reaction equation

HRID 253591 reaction equation
[NH2:1][CH2:2][CH2:3][O:4][C@@H:5]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=1)[C@@H:6]1[O:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1.CCN(CC)CC.Cl[C:34]([O:36][CH3:37])=[O:35].O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:25][C:21]1[CH:20]=[C:19]([C@H:5]([O:4][CH2:3][CH2:2][NH:1][C:34]([O:36][CH3:37])=[O:35])[C@@H:6]2[O:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]2)[CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 57786514(R)-tert-butyl 2-((S)-(2-aminoethoxy)(3-chlorophenyl)methyl)morpholine-4-carboxylate

Product 1

HCID 57786537(R)-tert-butyl 2-((S)-(3-chlorophenyl)(2-(methoxycarbonylamino)ethoxy)methyl)morpholine-4-carboxylateYield 6.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a solution of (R)-tert-butyl 2-((S)-(2-aminoethoxy)(3-chlorophenyl)methyl)morpholine-4-carboxylate (1.62 g, 4.38 mmol) and DMAP (280 mg) in dry CH2Cl2 (15 mL), Et3N (1.33 g, 13.14 mmol) was added. The resulting mixture was cooled to 0-5° C. in an ice-water bath and a solution of methyl chloroformate (2.06 g, 21.9 mmol) in dry CH2Cl2 (5 mL) was added dropwise. The reaction mixture was stirred for 1-2 h at 0-5° C. Tlc showed the starting material had disappeared. Water (30 mL) was added and the aqueous layer was extracted with CH2Cl2 (3×10 mL). The combined organic layers were washed with 10% aq citric acid (2×10 mL) and brine, dried over Na2SO4, filtered and concentrated to the crude product, which was purified by preparative HPLC to afford the desired product (120 mg, 6%). 1H NMR (MeOD) 1.45 (s, 9H), 2.80-2.92 (m, 2H), 3.0 (m, 1H), 3.60 (s, 3H), 4.15 (m, 2H), 4.25 (d, 1H), 7.20-7.35 (m, 4H).

Workup

  1. extractionthe aqueous layer was extracted with CH2Cl2 (3×10 mL)
  2. washThe combined organic layers were washed with 10% aq citric acid (2×10 mL) and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to the crude product, which
  6. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-07985eae5bab467690fffd180590f2be
Source dataset
uspto-grants-2011_01
Patent number
US07872028B2

Reaction notes

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