Acetaldehyde → HCID 178448301, compound

HRID 1007530Notes

Reaction equation

HRID 1007530 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C@@H:10]([NH:14][C@H:15]2[CH2:20][CH2:19][C@H:18]([C:21]3[CH:30]=[CH:29][C:24]4[NH:25][C:26](=[O:28])[O:27][C:23]=4[CH:22]=3)[CH2:17][CH2:16]2)[CH2:11][CH2:12][CH3:13])=[CH:4][CH:3]=1.[CH:31](=O)[CH3:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[CH2:31]([N:14]([C@@H:10]([CH2:11][CH2:12][CH3:13])[CH2:9][S:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C@H:15]1[CH2:16][CH2:17][C@H:18]([C:21]2[CH:30]=[CH:29][C:24]3[NH:25][C:26](=[O:28])[O:27][C:23]=3[CH:22]=2)[CH2:19][CH2:20]1)[CH3:32]

Participants

5

Reactant 3

HCID 177AcetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 178448302HCID 178448302, compound

Product 1

HCID 178448301HCID 178448301, compoundYield 67.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To (a) (S)-6-{trans-4-[1-(4-fluorophenylsulfanyl)pentan-2-ylamino]cyclohexyl}-3H-benzoxazol-2-one (292 mg, 0.687 mmol) in THF (10 mL) was added acetaldehyde (30 mg, 0.68 mmol) and 4 Å molecular sieves. After stirring for 0.25 hours, sodium triacetoxyborohydride (204 mg, 0.962 mmol) was added. The reaction mixture was stirred for 0.75 hours then concentrated under reduced pressure. The crude residue was taken up in methanol (10 mL), and solid NaOH was added until the pH was >8. The solution was concentrated under reduced pressure. Purification by flash chromatography (silica, 1:1 Hexanes:EtOAc) gave (b) (S)-6-{trans-4-[ethyl(1-(4-fluorophenylsulfanyl)-pentan-2-yl)amino]cyclohexyl}-3H-benzoxazol-2-one (210 mg, 67%), as a clear oil: IR (KBr): 3219, 2926, 1764, 1589 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.34 (m, 2H), 7.05-6.92 (m, 5H), 3.02 (m, 3H), 2.79 (m, 1H), 2.64 (m, 6H), 2.38 (m, 1H), 1.93-1.78 (m, 4H), 1.47-1.29 (m, 4H), 0.93 (t, J=5 Hz, 3H), 0.89 (t, J=6 Hz, 3H); API-MS (m/z): 457 [M+H]+; calcd for C26H33FN2O2S, 457.2325; found, 457.2324; HPLC: method C, 6.55 minutes (>99%), method D, 12.37 minutes (>99%).

Workup

  1. stirringThe reaction mixture was stirred for 0.75 hours
  2. concentrationthen concentrated under reduced pressure
  3. additionsolid NaOH was added until the pH was >8
  4. concentrationThe solution was concentrated under reduced pressure
  5. customPurification by flash chromatography (silica, 1:1 Hexanes:EtOAc)

Sources & evidence

ORD record
ord-d85e7b3082fb45a183861865e893b47b
Source dataset
uspto-grants-2004_09
Patent number
US06794402B2

Reaction notes

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