Acetic Acid → HCID 86591648, compound

HRID 2212982Notes

Reaction equation

HRID 2212982 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C@H:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[CH:16]=O.[CH3:18][NH:19][CH3:20].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO.C1COCC1>[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C@@H:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[CH2:16][N:19]([CH3:20])[CH3:18]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 11325241HCID 11325241, compound

Product 1

HCID 86591648HCID 86591648, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a room temperature solution of (1S,2S)-2-(5-iodo-1H-indol-3-yl)-cyclo-pentanecarbaldehyde (17.5 g, 51.6 mMol) in 200 mL of methanol was added with stirring dimethylamine (64 mL of a 2.0 M solution in THF, 128 mMol) followed by acetic acid (0.5 mL). After 15 min, NaBH(OAc)3 (12 g, 57 mMol) was added slowly. The resulting mixture was stirred 18 h and was then concentrated under vacuum. The residue was partitioned between ethyl acetate (400 mL) and aqueous NaHCO3 (300 mL). The organic layer was washed twice with aqueous NaHCO3 (250 mL). Every aqueous layer was extracted with ethyl acetate (50 mL) to make sure no product was left in aqueous. The combined organic extracts were then dried over MgSO4. Solvent was removed under vacuum and the residue was pump dried overnight to give crude trans [2-(5-iodo-1H-indol-3-yl)-cyclopentylmethyl]-dimethylamine (19.4 g, 100%) which was used directly for the next reaction without further purification. An analytical sample was prepared by crystallization from ethyl acetate. 1H NMR (400 MHz, methanol-d4) δ 7.86 (s, 1H), 7.30 (d, 1H), 7.14 (d, 1H), 7.02 (s, 1H), 2.80 (m, 1H), 2.27 (m, 3H), 2.12 (s, 6H), 2.10 (m, 2H), 1.79 (m, 3H), 1.46 (m, 1H); 13C NMR (400 MHz, methanol-d4), δ 137.6, 131.1, 130.5, 128.9, 123.2, 119.0, 114.6, 82.3, 66.2, 46.0, 45.6, 43.4, 35.0, 33.0, 25.2; HRMS (EI), exact mass calc'd for C16H21IN2 (M+H) 369.0828, found 369.0836.

Workup

  1. concentrationwas then concentrated under vacuum
  2. customThe residue was partitioned between ethyl acetate (400 mL) and aqueous NaHCO3 (300 mL)
  3. washThe organic layer was washed twice with aqueous NaHCO3 (250 mL)
  4. extractionEvery aqueous layer was extracted with ethyl acetate (50 mL)
  5. waitwas left in aqueous
  6. dry with materialThe combined organic extracts were then dried over MgSO4
  7. customSolvent was removed under vacuum
  8. customdried overnight

Sources & evidence

ORD record
ord-a4e9f508b6f74f0aa8042209f8aa4db4
Source dataset
uspto-grants-2006_09
Patent number
US07105516B2

Reaction notes

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