Acetyl chloride → tert-Butyl 1-acetyl-5-chlorospiro[indoline-3,4'-piperidine]-1'-carboxylate

HRID 706351Notes

Reaction equation

HRID 706351 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][C:15]2([C:25]3[C:20](=[CH:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[NH:19][CH2:18]2)[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].C(N(CC)CC)C>ClCCl>[C:5]([O:9][C:10]([N:12]1[CH2:13][CH2:14][C:15]2([C:25]3[C:20](=[CH:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[N:19]([C:1](=[O:3])[CH3:2])[CH2:18]2)[CH2:16][CH2:17]1)=[O:11])([CH3:8])([CH3:6])[CH3:7]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 46835581Tert-butyl 5-chlorospiro[indoline-3,4'-piperidine]-1'-carboxylate

Product 1

HCID 58046557tert-Butyl 1-acetyl-5-chlorospiro[indoline-3,4'-piperidine]-1'-carboxylateYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acetyl chloride (2.8 ml) was added dropwise to a stirred solution of 5-chlorospiro[indoline-3,4′-piperidine]-1′-carboxylic acid tert-butyl ester (9.8 g) and triethylamine (15 ml) in anhydrous dichloromethane (400 ml) under an atmosphere of nitrogen. The reaction was stirred for 1 h and was then quenched with saturated sodium bicarbonate solution (200 ml). The organic layer was dried over anhydrous sodium sulphate and concentrated in vacuo to yield 9.8 g (87%) of the desired amide as an off-white solid. M.p. 64-66° C. 1H NMR (400 MHz, CDCl3) δ 6:1 mixture of rotamers. Major rotamer 1.5 (9H, s), 1.70 (m, 2H), 1.85 (m, 2H), 2.25 (s, 3H), 2.85 (m, 2H), 3.90 (s, 2H), 4.2 (m, 2H), 6.97 (d, J=1 Hz, 1H), 7.20 (dd, J=7 & 1 Hz, 1H), 8.15 (d, J=7 Hz, 1H). Minor rotamer 1.5 (9H, s), 1.70 (m, 2H), 1.85 (m, 2H), 2.45 (s, 3H), 2.85 (m, 2H), 4.05 (s, 2H), 4.2 (m, 2H), 7.2 (d, J=1 Hz, 1H), 7.25 (dd, J=7 & 1 Hz, 1H), 7.48 (d, J=7 Hz, 1H).

Workup

  1. customwas then quenched with saturated sodium bicarbonate solution (200 ml)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-716af16337de4463ae5428fd85fedf81
Source dataset
uspto-grants-2015_11
Patent number
US09174987B2

Reaction notes

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