Methyl chloroformate → Tert-butyl 3-(2-(methoxycarbonyl)aminoethoxy)-3-(3-chlorophenyl)propyl(methyl)carbamate

HRID 426037Notes

Reaction equation

HRID 426037 reaction equation
[NH2:1][CH2:2][CH2:3][O:4][CH:5]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=1)[CH2:6][CH2:7][N:8]([CH3:16])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12].CCN(CC)CC.Cl[C:32]([O:34][CH3:35])=[O:33]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:35][O:34][C:32]([NH:1][CH2:2][CH2:3][O:4][CH:5]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=1)[CH2:6][CH2:7][N:8]([CH3:16])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:12])[CH3:13])=[O:33]

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 59364336Tert-butyl 3-(2-aminoethoxy)-3-(3-chlorophenyl)propyl(methyl)carbamate

Product 1

HCID 66704353Tert-butyl 3-(2-(methoxycarbonyl)aminoethoxy)-3-(3-chlorophenyl)propyl(methyl)carbamateYield 40%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a 0° C. solution of tert-butyl 3-(2-aminoethoxy)-3-(3-chlorophenyl)propyl(methyl)carbamate (6 g, 4.11 mmol), Et3N (1.25 g, 12.3 mL), DMAP (0.25 g, 2.06 mmol) in dry CH2Cl2 (100 mL), methyl chloroformate (1.9 g, 20.6 mmol) in dry CH2Cl2 (30 mL) was added drop wise. After addition, the reaction mixture was stirred for 1-2 h at 0-5° C. The reaction was quenched with water. The aqueous layer was extracted with CH2Cl2, the combined organic layers were washed with 10% citric acid and brine, then dried over Na2SO4, filtered and concentrated to the crude product. The crude product was purified by silica gel to afford tert-butyl 3-(2-(methoxycarbonyl)aminoethoxy)-3-(3-chlorophenyl)propyl(methyl)carbamate (600 mg, 40%). 1H NMR (CDCl3, 400 MHz) δ 1.49 (s, 9H), 1.83 (m, 2H), 2.80 (s, 3H), 3.31 (m, 7H), 3.65 (s, 3H), 4.13 (m, 1H), 7.26 (m, 4H).

Workup

  1. additionAfter addition
  2. customThe reaction was quenched with water
  3. extractionThe aqueous layer was extracted with CH2Cl2
  4. washthe combined organic layers were washed with 10% citric acid and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to the crude product
  8. customThe crude product was purified by silica gel

Sources & evidence

ORD record
ord-6ec61189bba342e1b310f461819027cf
Source dataset
uspto-grants-2012_01
Patent number
US08106221B2

Reaction notes

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