Benzyl chloroformate → benzyl (2S)-2-(hydroxymethyl)morpholine-4-carboxylate

HRID 1518767Notes

Reaction equation

HRID 1518767 reaction equation
Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].CCN(C(C)C)C(C)C.[NH:21]1[CH2:26][CH2:25][O:24][C@H:23]([CH2:27][OH:28])[CH2:22]1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOC(C)=O>[OH:28][CH2:27][C@H:23]1[O:24][CH2:25][CH2:26][N:21]([C:2]([O:4][CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:3])[CH2:22]1

Participants

7

Reactant 4

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 1512575(S)-morpholin-2-ylmethanol

Product 1

HCID 1514139benzyl (2S)-2-(hydroxymethyl)morpholine-4-carboxylateYield 54%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Benzyl chloroformate (0.598 mL, 0.956 mmol, 3.5 equiv) was added slowly to a solution of DIPEA (0.477 mL, 2.73 mmol, 10 equiv) and 2.20.1a (64 mg, 0.547 mmol) in DCM (2 mL). The resulting mixture was stirred at room temperature for 4 hours. EtOAc and saturated aqueous NaHCO3 solution were then added to the mixture. The phases were separated and the organic layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The remaining oil was purified by silica gel column chromatography (EtOAc/heptane, 40-100%) to give product 74 mg (54% yield). MS m/z (M+1) 252.2.

Workup

  1. customThe phases were separated
  2. extractionthe organic layer was extracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe remaining oil was purified by silica gel column chromatography (EtOAc/heptane, 40-100%)

Sources & evidence

ORD record
ord-e91648ec91cb4f7eb9ea90a6552e928b
Source dataset
uspto-grants-2015_07
Patent number
US09072696B2

Reaction notes

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