Acetic Anhydride → (S)-N-(3-Chloro-2-hydroxypropyl)acetamide

HRID 2188341Notes

Reaction equation

HRID 2188341 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH2:10][C@H:11]([OH:14])[CH2:12][Cl:13].[C:15](OC(=O)C)(=[O:17])[CH3:16]>C1COCC1>[C:15]([NH:9][CH2:10][C@H:11]([OH:14])[CH2:12][Cl:13])(=[O:17])[CH3:16]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 1350101-Amino-3-chloro-2-propanol hydrochloride, (S)-

Product 1

HCID 11105542(S)-N-(3-Chloro-2-hydroxypropyl)acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (10.5ml, 75.3 mmol, 1.11 eq) is added to a slurry of (S)-1-amino-3-chloro-2-propanol hydrochloride (V, EXAMPLE 1, 9,938 g, 68.059 mmol) in THF (80 ml) at −40° and the mixture stirred for 5 min at −40°. Acetic anhydride (6.78 ml, 71.86 mmol, 1.056 eq) is then added at −40° and the mixture allowed to warm to 20-25° over 1.5 hrs. The precipitate is removed by filtration with reduced pressure and washed with THF. The filtrate is treated with magnesol (5.69 g), which is removed by filtration with reduced pressure and washed with THF (2×60 ml). The filtrate is then concentrated under reduced pressure. The concentrate is purified by flash chromatography (silica gel; eluting with a gradient of 75-100% ethyl acetate/cyclohexane) to give the title compound, NMR (CDCl3) 2.03, 3.32, 3.50-3.57, 3.55, 3.91-4.13, 5.01 and 7.09 δ; CMR (CDCl3) 23.00, 43.31, 46.52, 70.65 and 172.40 δ; MS (CI, NH3), M/Z (relative intensity), 171 (41.6), 169 (100), 154 (22.4), 152 (48.1); [a]25D=−7.44 (c =1.00, H2O).

Workup

  1. temperatureto warm to 20-25° over 1.5 hrs
  2. customThe precipitate is removed by filtration with reduced pressure
  3. washwashed with THF
  4. additionThe filtrate is treated with magnesol (5.69 g), which
  5. customis removed by filtration with reduced pressure
  6. washwashed with THF (2×60 ml)
  7. concentrationThe filtrate is then concentrated under reduced pressure
  8. customThe concentrate is purified by flash chromatography (silica gel
  9. washeluting with a gradient of 75-100% ethyl acetate/cyclohexane)

Sources & evidence

ORD record
ord-0a1527c8cf7b4d6bb492ef6705b1c2cb
Source dataset
uspto-grants-2002_06
Patent number
US06410788B1

Reaction notes

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