Acetaldehyde → HCID 16723074, compound

HRID 555263Notes

Reaction equation

HRID 555263 reaction equation
[CH2:1]([O:3][C:4](=[O:28])[CH2:5][CH2:6][NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([N:16]2[CH2:22][C:21]3([CH3:24])[CH2:23][CH:17]2[CH2:18][C:19]([CH3:26])([CH3:25])[CH2:20]3)=[O:15])=[CH:10][C:9]=1[NH2:27])[CH3:2].C(=O)C.CN1C(=O)[CH2:36][CH2:35][CH2:34]1>>[CH2:1]([O:3][C:4](=[O:28])[CH2:5][CH2:6][N:7]1[C:8]2[CH:13]=[CH:12][C:11]([C:14]([N:16]3[CH2:22][C:21]4([CH3:24])[CH2:23][CH:17]3[CH2:18][C:19]([CH3:26])([CH3:25])[CH2:20]4)=[O:15])=[CH:10][C:9]=2[N:27]=[C:34]1[CH2:35][CH3:36])[CH3:2]

Participants

4

Reactant 3

HCID 177AcetaldehydeHCID 13387N-methyl-2-pyrrolidoneHCID 66987201HCID 66987201, compound

Product 1

HCID 16723074HCID 16723074, compoundYield 38%

Conditions

Temperature
50 °C

Procedure

To a solution of 3-[2-amino-4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenylamino]-propionic acid ethyl ester (250 mg, 0.645 mmol) in dry NMP (10 mL) at room temperature under an inert atmosphere of nitrogen was added approx. 200 mg of molecular sieve 4 Å followed by acetaldehyde (93 uL, 1.29 mmol). The mixture was stirred for 16 hrs at 50° C. The reaction was quenched by the addition of water (100 mL) followed by extraction with diethyl ether (3×100 mL). The combined organic phases were washed with brine (4×200 mL), dried (MgSO4), filtered, and evaporated in vacuo. The resulting oil was purified by preparative HPLC, dried in vacuo at 50° C. affording 104 mg (38%) of the title compound as brown oil. MS-ESI m/z 426; 1H NMR (400 MHz, CDCl3) δ 0.88-1.06 (m, 6H), 1.11-1.23 (m, 7H), 1.24-1.28 (m) and 1.55-1.65 (m, 1H), 1.36-1.45 (m, 2H), 1.50 (t, 3H), 1.74-1.81 (m, 1H), 2.23-2.30 (m) and 3.12-3.20 (m, 1H), 2.81 (t, 2H), 2.96 (q, 2H), 3.22-3.35 (m, 1H), 3.32 (dd) and 3.62 (dd, 1H), 4.03-4.07 (m) and 4.63-4.67 (m, 1H), 4.13 (q, 2H), 4.45 (dt, 2H), 7.32-7.46 (m, 2H), 7.84 (d, 1H).

Workup

  1. customThe reaction was quenched by the addition of water (100 mL)
  2. extractionfollowed by extraction with diethyl ether (3×100 mL)
  3. washThe combined organic phases were washed with brine (4×200 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe resulting oil was purified by preparative HPLC
  8. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-9a3a1282f3404bc6891cf0fc7dc38d5a
Source dataset
uspto-grants-2011_11
Patent number
US08053431B2

Reaction notes

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