Acetic Acid → HCID 70686336, compound

HRID 2364900Notes

Reaction equation

HRID 2364900 reaction equation
[NH2:1][C:2]1[C:3]([C:85]([NH:87][CH2:88][CH2:89][O:90][CH2:91][CH2:92][O:93][CH2:94][CH2:95][O:96][CH2:97][CH2:98][O:99][CH2:100][CH2:101][O:102][CH2:103][CH2:104][O:105][CH2:106][CH2:107][O:108][CH2:109][CH2:110][O:111][CH2:112][CH2:113][O:114][CH2:115][CH2:116][O:117][CH2:118][CH2:119][O:120][CH2:121][CH2:122][O:123][CH2:124][CH2:125][O:126][CH2:127][CH2:128][O:129][CH2:130][CH2:131][O:132][CH2:133][CH2:134][O:135][CH2:136][CH2:137][O:138][CH2:139][CH2:140][O:141][CH2:142][CH2:143][O:144][CH2:145][CH2:146][O:147][CH2:148][CH2:149][O:150][CH2:151][CH2:152][O:153][CH2:154][CH2:155][O:156][CH2:157][CH2:158][O:159][CH3:160])=[O:86])=[N:4][C:5]([NH2:84])=[C:6]([C:8]([NH:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33][O:34][CH2:35][CH2:36][O:37][CH2:38][CH2:39][O:40][CH2:41][CH2:42][O:43][CH2:44][CH2:45][O:46][CH2:47][CH2:48][O:49][CH2:50][CH2:51][O:52][CH2:53][CH2:54][O:55][CH2:56][CH2:57][O:58][CH2:59][CH2:60][O:61][CH2:62][CH2:63][O:64][CH2:65][CH2:66][O:67][CH2:68][CH2:69][O:70][CH2:71][CH2:72][O:73][CH2:74][CH2:75][O:76][CH2:77][CH2:78][O:79][CH2:80][CH2:81][O:82][CH3:83])=[O:9])[N:7]=1.[CH:161](=O)[CH2:162][CH3:163].[CH3:165][C:166](O)=O.[C:169](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:161]([NH:84][C:5]1[C:6]([C:8]([NH:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33][O:34][CH2:35][CH2:36][O:37][CH2:38][CH2:39][O:40][CH2:41][CH2:42][O:43][CH2:44][CH2:45][O:46][CH2:47][CH2:48][O:49][CH2:50][CH2:51][O:52][CH2:53][CH2:54][O:55][CH2:56][CH2:57][O:58][CH2:59][CH2:60][O:61][CH2:62][CH2:63][O:64][CH2:65][CH2:66][O:67][CH2:68][CH2:69][O:70][CH2:71][CH2:72][O:73][CH2:74][CH2:75][O:76][CH2:77][CH2:78][O:79][CH2:80][CH2:81][O:82][CH3:83])=[O:9])=[N:7][C:2]([NH:1][CH2:169][CH2:166][CH3:165])=[C:3]([C:85]([NH:87][CH2:88][CH2:89][O:90][CH2:91][CH2:92][O:93][CH2:94][CH2:95][O:96][CH2:97][CH2:98][O:99][CH2:100][CH2:101][O:102][CH2:103][CH2:104][O:105][CH2:106][CH2:107][O:108][CH2:109][CH2:110][O:111][CH2:112][CH2:113][O:114][CH2:115][CH2:116][O:117][CH2:118][CH2:119][O:120][CH2:121][CH2:122][O:123][CH2:124][CH2:125][O:126][CH2:127][CH2:128][O:129][CH2:130][CH2:131][O:132][CH2:133][CH2:134][O:135][CH2:136][CH2:137][O:138][CH2:139][CH2:140][O:141][CH2:142][CH2:143][O:144][CH2:145][CH2:146][O:147][CH2:148][CH2:149][O:150][CH2:151][CH2:152][O:153][CH2:154][CH2:155][O:156][CH2:157][CH2:158][O:159][CH3:160])=[O:86])[N:4]=1)[CH2:162][CH3:163]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 527PropanalHCID 5049666Sodium triacetoxyborohydrideHCID 70686334HCID 70686334, compound

Product 1

HCID 70686336HCID 70686336, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of the above bis-amide 5 (crude, 2.15 g, 0.367 mmol) in anhyd 1,2-dichloroethane (20 mL), propionaldehyde (0.265 mL, 3.67 mmol) and HOAc (0.263 mL, 4.56 mmol) were added at ice-bath temperature while stirring in an atmosphere of argon. Then sodium triacetoxyborohydride (0.779 g, 3.68 mmol) was added in small portions over a 15 min period, resulting reddish suspension was slowly allowed to warm to room temperature and stirred overnight under argon. The reaction was quenched by a slow addition of saturated NaHCO3 (20 mL) at 0° C. The biphasic mixture was stirred for 15 min and extracted with CHCl3 (3×25 mL). The combined organic extracts were washed with water and brine (50 mL each) and then dried over Na2SO4. Solvents were removed in vacuo and the crude product (0.945 g) was subjected purification by preparative RP-HPLC (Sunfire, 5-95% B/10 min). The pure fractions were concentrated in vacuo, the residue was co-evaporated with CH3CN (3×10 mL), and then dried under high vacuum to give 4 (0.281 g, 33%) as a brick-red sticky solid: 1H NMR (CDCl3) characteristic br s at δ 3.64 for poly(ethylene glycol) moiety; RP-HPLC (264 nm) 91% (tR=19.2 min); RP-LC/MS (ESI) m/z 567.4 (M+H)+, 589.4 (M+Na)+ (tR=5.17 min). HRMS (ESI) m/z calculated for C110H218N6O56 (M+2H)2+ 1211.7345, found 1211.7343; calculated for C110H217N6O56Na (M+H+Na)2+ 1222.7254, found 1222.7256; calculated for C110H216N6O56Na2 (M+2Na)2+ 1233.7164, found 1233.7173.

Workup

  1. customresulting reddish suspension
  2. stirringstirred overnight under argon
  3. customThe reaction was quenched by a slow addition of saturated NaHCO3 (20 mL) at 0° C
  4. stirringThe biphasic mixture was stirred for 15 min
  5. extractionextracted with CHCl3 (3×25 mL)
  6. washThe combined organic extracts were washed with water and brine (50 mL each)
  7. dry with materialdried over Na2SO4
  8. customSolvents were removed in vacuo
  9. custompurification by preparative RP-HPLC (Sunfire, 5-95% B/10 min)
  10. concentrationThe pure fractions were concentrated in vacuo
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-51db4ac591224de285c824b64e221b1a
Source dataset
uspto-grants-2014_04
Patent number
US08697033B2

Reaction notes

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